Carlos Rosales | Universidad Nacional Autónoma de México (original) (raw)

Papers by Carlos Rosales

Research paper thumbnail of Constitutive Innate Immunity of Migrant and Resident Long-Nosed Bats (Leptonycteris yerbabuenae) in the Drylands of Mexico

Diversity

In contrast to birds, the relationship between migration and immunity has been scarcely studied i... more In contrast to birds, the relationship between migration and immunity has been scarcely studied in bats. We examined how the expression of the humoral portion of the constitutive immunity varied in a bat with partial, sex-biased migration: the lesser long-nosed bat (Leptonycteris yerbabuenae (Phyllostomidae)). The lesser long-nosed bat is a nectarivorous species distributed in the arid and semi-arid regions of North and Central America. We evaluated the bacteria-killing abilities (BKAs) of the plasma of male and female lesser long-nosed bats on the Pacific coast in different periods of the year. Because adult males are resident, they were used to explore the effect of reproductive activity on BKA, and we predicted higher values in mating males (i.e., individuals presenting scrotal testicles and a fresh dorsal patch). In contrast to males, most females migrate to cactus deserts in northern Mexico during pregnancy and lactation, and then return to the dry forests of west-central Mexic...

Research paper thumbnail of Neutrophil to lymphocyte ratio and principal component analysis offer prognostic advantage for dogs with mammary tumors

Frontiers in Veterinary Science, 2023

IntroductionIn veterinary medicine, cancer is the leading cause of death in companion animals, an... more IntroductionIn veterinary medicine, cancer is the leading cause of death in companion animals, and mammary gland tumors represent the most common neoplasm in female dogs. Several epidemiological risk factors, such as age, breed, hormones, diet, and obesity have been reported to be relevant for canine mammary tumors. Nowadays, the gold standard for diagnosis of canine mammary tumors is the pathological examination of the suspected tissue. However, tumor grade can only be assessed after surgical removal or biopsy of the altered tissue. Therefore, in cases of tumors that could be surgically removed, it would be very helpful to be able to predict the biological behavior of the tumor, before performing any surgery. Since, inflammation constitutes part of the tumor microenvironment and it influences each step of tumorigenesis, cellular and biochemical blood markers of systemic inflammation, such as the neutrophil to lymphocyte ratio (NLR) and the albumin to globulin ratio (AGR) have been ...

Research paper thumbnail of Cytotoxicity assessment of three endodontic sealing cements used in periapical surgery. In vitro study

Revista Odontológica Mexicana, 2017

Introduction: Presently there are many retro lling materials in the market, nevertheless, little ... more Introduction: Presently there are many retro lling materials in the market, nevertheless, little is known about their toxicity on gingival broblasts. Objective: To assess cytotoxicity of three materials to human gingival fibroblasts and L929 mouse fibroblasts cell line. Material and methods: EndoSequence ® BC RRM TM (ERRM; root repair material), white MTA Angelus ® (MTA) and intermediate restoration material (IRM ®) conditioned media were obtained when materials were freshly mixed, at setting time and after 1, 24 and 72 hours of setting time. Cell morphology was assessed with light microscopy and cell viability was assessed through mitochondrial metabolic activity with 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide (MTT). Statistical analysis was conducted with ANOVA. Results: We found that ERRM material did not exhibit cytotoxic effects on used broblast, nevertheless, MTA and IRM ® respectively exhibited moderate and severe cytotoxicity, thus indicating the materials were not fully harmless. Conclusion: Bioceramic cements like ERRM could be considered the most compatible retro lling-materials.

Research paper thumbnail of Regression of Human Papillomavirus Intraepithelial Lesions Is Induced by MVA E2 Therapeutic Vaccine

Human Gene Therapy, 2014

Human papilloma viruses can induce warts, condylomas, and other intraepithelial cervical lesions ... more Human papilloma viruses can induce warts, condylomas, and other intraepithelial cervical lesions that can progress to cancer. Cervical cancer is a serious problem in developing countries because early detection is difficult, and thus proper early treatment is many times missing. In this phase III clinical trial, we evaluated the potential use of MVA E2 recombinant vaccinia virus to treat intraepithelial lesions associated with papillomavirus infection. A total of 1176 female and 180 male patients with intraepithelial lesions were studied. They were injected with 10 7 MVA E2 virus particles directly into their uterus, urethra, vulva, or anus. Patients were monitored by colposcopy and cytology. Immune response was determined by measuring the antibody titer against MVA E2 virus and by analyzing the cytotoxic activity against cancer cells bearing papillomavirus DNA. Papillomavirus was determined by the Hybrid Capture method or by polymerase chain reaction analysis. By histology, 1051 (89.3%) female patients showed complete elimination of lesions after treatment with MVA E2. In 28 (2.4%) female patients, the lesion was reduced to CIN 1. Another 97 (8.3%) female patients presented isolated koilocytes after treatment. In men, all lesions were completely eliminated. All MVA E2-treated patients developed antibodies against the MVA E2 vaccine and generated a specific cytotoxic response against papilloma-transformed cells. Papillomavirus DNA was not detected after treatment in 83% of total patients treated. MVA E2 did not generate any apparent side effects. These data suggest that therapeutic vaccination with MVA E2 vaccine is an excellent candidate to stimulate the immune system and generate regression in intraepithelial lesions when applied locally.

Research paper thumbnail of Modification of Proliferation and Apoptosis in Breast Cancer Cells by Exposure of Antioxidant Nanoparticles Due to Modulation of the Cellular Redox State Induced by Doxorubicin Exposure

Pharmaceutics, 2021

In this report, we investigated whether the use of chitosan-carrying-glutathione nanoparticles (C... more In this report, we investigated whether the use of chitosan-carrying-glutathione nanoparticles (CH-GSH NPs) can modify proliferation and apoptosis, and reduce cell damage induced by doxorubicin on breast cancer cells. Doxorubicin is a widely used antineoplasic agent for the treatment of various types of cancer. However, it is also a highly toxic drug because it induces oxidative stress. Thus, the use of antioxidant molecules has been considered to reduce the toxicity of doxorubicin. CH-GSH NPs were characterized in size, zeta potential, concentration, and shape. When breast cancer cells were treated with CH-GSH nanoparticles, they were localized in the cellular cytoplasm. Combined doxorubicin exposure with nanoparticles increased intracellular GSH levels. At the same time, decreasing levels of reactive oxygen species and malondialdehyde were observed and modified antioxidant enzyme activity. Levels of the Ki67 protein were evaluated as a marker of cell proliferation and the activity...

Research paper thumbnail of Neutrophils Actively Contribute to Obesity-Associated Inflammation and Pathological Complications

Cells

Obesity is characterized by an increase in body weight associated with an exaggerated enlargement... more Obesity is characterized by an increase in body weight associated with an exaggerated enlargement of the adipose tissue. Obesity has serious negative effects because it is associated with multiple pathological complications such as type 2 diabetes mellitus, cardiovascular diseases, cancer, and COVID-19. Nowadays, 39% of the world population is obese or overweight, making obesity the 21st century epidemic. Obesity is also characterized by a mild, chronic, systemic inflammation. Accumulation of fat in adipose tissue causes stress and malfunction of adipocytes, which then initiate inflammation. Next, adipose tissue is infiltrated by cells of the innate immune system. Recently, it has become evident that neutrophils, the most abundant leukocytes in blood, are the first immune cells infiltrating the adipose tissue. Neutrophils then get activated and release inflammatory factors that recruit macrophages and other immune cells. These immune cells, in turn, perpetuate the inflammation state...

Research paper thumbnail of The Antibody Receptor Fc Gamma Receptor IIIb Induces Calcium Entry via Transient Receptor Potential Melastatin 2 in Human Neutrophils

Frontiers in Immunology, 2021

Human neutrophils express two unique antibody receptors for IgG, the FcγRIIa and the FcγRIIIb. Fc... more Human neutrophils express two unique antibody receptors for IgG, the FcγRIIa and the FcγRIIIb. FcγRIIa contains an immunoreceptor tyrosine-based activation motif (ITAM) sequence within its cytoplasmic tail, which is important for initiating signaling. In contrast, FcγRIIIb is a glycosylphosphatidylinositol (GPI)-linked receptor with no cytoplasmic tail. Although, the initial signaling mechanism for FcγRIIIb remains unknown, it is clear that both receptors are capable of initiating distinct neutrophil cellular functions. For example, FcγRIIa is known to induce an increase in L-selectin expression and efficient phagocytosis, while FcγRIIIb does not promote these responses. In contrast, FcγRIIIb has been reported to induce actin polymerization, activation of β1 integrins, and formation of neutrophils extracellular traps (NET) much more efficiently than FcγRIIa. Another function where these receptors seem to act differently is the increase of cytoplasmic calcium concentration. It has be...

Research paper thumbnail of Editorial: Integrative Approaches to the Molecular Physiology of Inflammation

Frontiers in Physiology, 2018

Research paper thumbnail of Fcγ Receptor Heterogeneity in Leukocyte Functional Responses

Frontiers in Immunology, 2017

FiGURe 1 | Mouse Fcγ receptors (FcγRs). Schematic illustration of mouse receptors for IgG. FcγRs ... more FiGURe 1 | Mouse Fcγ receptors (FcγRs). Schematic illustration of mouse receptors for IgG. FcγRs are shown relative to the cell membrane (yellow line) and together with their respective signaling subunits. γ2, FcR gamma subunit dimer; β2m, beta-2 microglobulin; ITAM, immunoreceptor tyrosine-based activation motif (green rectangle); ITIM, immunoreceptor tyrosine-based inhibition motif (red rectangle); FcRn, neonatal Fc receptor. TRIM21 is a cytosolic receptor. 2 Rosales Each FcγR Activates Distinct Functions

Research paper thumbnail of New Insights on NETosis Induced by Entamoeba histolytica: Dependence on ROS from Amoebas and Extracellular MPO Activity

Antioxidants

NETosis is a neutrophil process involving sequential steps from pathogen detection to the release... more NETosis is a neutrophil process involving sequential steps from pathogen detection to the release of DNA harboring antimicrobial proteins, including the central generation of NADPH oxidase dependent or independent ROS. Previously, we reported that NETosis triggered by Entamoeba histolytica trophozoites is independent of NADPH oxidase activity in neutrophils, but dependent on the viability of the parasites and no ROS source was identified. Here, we explored the possibility that E. histolytica trophozoites serve as the ROS source for NETosis. NET quantitation was performed using SYTOX® Green assay in the presence of selective inhibitors and scavengers. We observed that respiratory burst in neutrophils was inhibited by trophozoites in a dose dependent manner. Mitochondrial ROS was not also necessary, as the mitochondrial scavenger mitoTEMPO did not affect the process. Surprisingly, ROS-deficient amoebas obtained by pre-treatment with pyrocatechol were less likely to induce NETs. Additi...

Research paper thumbnail of Fc receptor functions in host and immune regulation

Revista de investigación clínica

Specific receptors for antibody, named Fc Receptors are proteins found on the surface of leukocyt... more Specific receptors for antibody, named Fc Receptors are proteins found on the surface of leukocytes. Fc receptors contribute to the protective functions of the immune system, by binding to antibodies that are attached to infected cells or invading pathogens. Fc receptor activity stimulates phagocytic or cytotoxic cells to destroy microbes, or infected cells by antibody-mediated phagocytosis or antibody-dependent cell-mediated cytotoxicity. This review describes the main types of Fc receptors and the signal transduction pathways that are initiated by them in various leukocytes, with emphasis on activation of phagocytosis. New findings on the regulatory role of Fc receptors on immune function are also discussed.

Research paper thumbnail of Neutrophils in Cancer: Two Sides of the Same Coin

Journal of Immunology Research, 2015

Neutrophils are the most abundant leukocytes in blood and are considered to be the first line of ... more Neutrophils are the most abundant leukocytes in blood and are considered to be the first line of defense during inflammation and infections. In addition, neutrophils are also found infiltrating many types of tumors. Tumor-associated neutrophils (TANs) have relevant roles in malignant disease. Indeed neutrophils may be potent antitumor effector cells. However, increasing clinical evidence shows TANs correlate with poor prognosis. The tumor microenvironment controls neutrophil recruitment and in turn TANs help tumor progression. Hence, TANs can be beneficial or detrimental to the host. It is the purpose of this review to highlight these two sides of the neutrophil coin in cancer and to describe recent studies that provide some light on the mechanisms for neutrophil recruitment to the tumor, for neutrophils supporting tumor progression, and for neutrophil activation to enhance their antitumor functions.

Research paper thumbnail of Differential Use of Human Neutrophil FcγReceptors for Inducing Neutrophil Extracellular Trap Formation

Journal of Immunology Research, 2016

Neutrophils (PMN) are the most abundant leukocytes in the blood. PMN migrate from the circulation... more Neutrophils (PMN) are the most abundant leukocytes in the blood. PMN migrate from the circulation to sites of infection, where they are responsible for antimicrobial functions. PMN use phagocytosis, degranulation, and formation of neutrophil extracellular traps (NETs) to kill microbes. NETs are fibers composed of chromatin and neutrophil-granule proteins. Several pathogens, including bacteria, fungi, and parasites, and also some pharmacological stimuli such as phorbol 12-myristate 13-acetate (PMA) are efficient inducers of NETs. Antigen-antibody complexes are also capable of inducing NET formation. However the particular Fcγreceptor involved in triggering this function is a matter of controversy. In order to provide some insight into what Fcγreceptor is responsible for NET formation, each of the two human Fcγreceptors was stimulated individually by specific monoclonal antibodies and NET formation was evaluated. FcγRIIa cross-linking did not promote NET formation. Cross-linking other...

Research paper thumbnail of Neutrophils in Cancer: Two Sides of the Same Coin

Neutrophils are the most abundant leukocytes in blood and are considered to be the first line of ... more Neutrophils are the most abundant leukocytes in blood and are considered to be the first line of defense during inflammation and infections. In addition, neutrophils are also found infiltrating many types of tumors. Tumor-associated neutrophils (TANs) have relevant roles in malignant disease. Indeed neutrophils may be potent antitumor effector cells. However, increasing clinical evidence shows TANs correlate with poor prognosis. The tumor microenvironment controls neutrophil recruitment and in turn TANs help tumor progression. Hence, TANs can be beneficial or detrimental to the host. It is the purpose of this review to highlight these two sides of the neutrophil coin in cancer and to describe recent studies that provide some light on the mechanisms for neutrophil recruitment to the tumor, for neutrophils supporting tumor progression, and for neutrophil activation to enhance their antitumor functions.

Research paper thumbnail of Editorial: Phagocytosis: Molecular Mechanisms and Physiological Implications

Frontiers in Immunology, Sep 11, 2020

Research paper thumbnail of Phagocytosis

Reference Module in Biomedical Sciences

Research paper thumbnail of Cellular and Molecular Mechanisms of Insect Immunity

Insect Physiology and Ecology, 2017

Multicellular organisms constantly encounter potentially harmful microorganisms. Although insects... more Multicellular organisms constantly encounter potentially harmful microorganisms. Although insects lack an adaptive immune system, they do have powerful means of fighting infections. Cellular responses involve phagocytosis of bacteria and encapsulation of parasites. In addition, insects can mount a humoral response against pathogens. This is characterized by the secretion of antimicrobial peptides into the hemolymph. Recognition of foreign pathogens involves specific receptors for sensing infection. These include peptidoglycan recognition proteins (PGRPs) and β-glucan recognition proteins (βGRPs). Engagement of these receptors starts signaling pathways that activate the genes that encode antimicrobial peptides. These pathways include the Toll, the Imd, and the JAK-STAT. This chapter describes the innate immunity of insects including both the cellular and humoral responses to bacteria, fungi, and parasites. In addition, recent advances in insect antivirus immune responses are discussed.

Research paper thumbnail of Phosphatidylinositol 3-kinase mediates integrin-dependent NF-κ B and MAPK activation through separate signaling pathways Merit

Research paper thumbnail of Immune Response to the Enteric Parasite Entamoeba histolytica

Physiology

Entamoeba histolytica is a protozoan parasite responsible for amoebiasis, a disease with a high p... more Entamoeba histolytica is a protozoan parasite responsible for amoebiasis, a disease with a high prevalence in developing countries. Establishing an amoebic infection involves interplay between pathogenic factors for invasion and tissue damage, and immune responses for protecting the host. Here, we review the pathogenicity of E. histolytica and summarize the latest knowledge on immune response and immune evasion mechanisms during amoebiasis.

Research paper thumbnail of Fc Receptors: cell activators of antibody functions

Advances in Bioscience and Biotechnology, Apr 1, 2013

At the onset of an infection early defense systems, such as complement, get into action. Speciali... more At the onset of an infection early defense systems, such as complement, get into action. Specialized leukocytes (white blood cells) of the innate immune system, including monocytes, macrophages, and neutrophils also participate as a first line of defense against infections. These early responses are rapid but not very specific and are usually not enough to clear completely many infections. The adaptive immune system is also needed to finish the job against many microorganisms. Antibody molecules, produced during the adaptive immune response, are crucial for preventing recurrent infections. Although, IgG antibodies are essential for controlling infections, these molecules do not directly damage the microorganisms they recognize. Today, it is established that leukocytes of the innate immune system are responsible for the protective effects of these antibodies. IgG molecules bind to their cognate antigens and are in turn recognized by specific receptors (Fcγ receptors) on the membrane of leukocytes. Crosslinking these receptors on the surface of leukocytes leads to activation of several effector cell functions. These effector functions are geared toward the destruction of microbial pathogens and the induction of an inflammatory state that is beneficial during infections. However, in autoimmune diseases, antibodies can direct these effector functions against normal tissues and cause severe tissue damage. In recent years, several factors that can modulate the IgG-FcγR interaction have been elucidated. In this review, we describe the main types of Fcγ receptors, and our current view of how antibody variants interact with these receptors to initiate different cell responses. In addition, new findings on the signaling role of individual Fcγ receptors are also discussed.

Research paper thumbnail of Constitutive Innate Immunity of Migrant and Resident Long-Nosed Bats (Leptonycteris yerbabuenae) in the Drylands of Mexico

Diversity

In contrast to birds, the relationship between migration and immunity has been scarcely studied i... more In contrast to birds, the relationship between migration and immunity has been scarcely studied in bats. We examined how the expression of the humoral portion of the constitutive immunity varied in a bat with partial, sex-biased migration: the lesser long-nosed bat (Leptonycteris yerbabuenae (Phyllostomidae)). The lesser long-nosed bat is a nectarivorous species distributed in the arid and semi-arid regions of North and Central America. We evaluated the bacteria-killing abilities (BKAs) of the plasma of male and female lesser long-nosed bats on the Pacific coast in different periods of the year. Because adult males are resident, they were used to explore the effect of reproductive activity on BKA, and we predicted higher values in mating males (i.e., individuals presenting scrotal testicles and a fresh dorsal patch). In contrast to males, most females migrate to cactus deserts in northern Mexico during pregnancy and lactation, and then return to the dry forests of west-central Mexic...

Research paper thumbnail of Neutrophil to lymphocyte ratio and principal component analysis offer prognostic advantage for dogs with mammary tumors

Frontiers in Veterinary Science, 2023

IntroductionIn veterinary medicine, cancer is the leading cause of death in companion animals, an... more IntroductionIn veterinary medicine, cancer is the leading cause of death in companion animals, and mammary gland tumors represent the most common neoplasm in female dogs. Several epidemiological risk factors, such as age, breed, hormones, diet, and obesity have been reported to be relevant for canine mammary tumors. Nowadays, the gold standard for diagnosis of canine mammary tumors is the pathological examination of the suspected tissue. However, tumor grade can only be assessed after surgical removal or biopsy of the altered tissue. Therefore, in cases of tumors that could be surgically removed, it would be very helpful to be able to predict the biological behavior of the tumor, before performing any surgery. Since, inflammation constitutes part of the tumor microenvironment and it influences each step of tumorigenesis, cellular and biochemical blood markers of systemic inflammation, such as the neutrophil to lymphocyte ratio (NLR) and the albumin to globulin ratio (AGR) have been ...

Research paper thumbnail of Cytotoxicity assessment of three endodontic sealing cements used in periapical surgery. In vitro study

Revista Odontológica Mexicana, 2017

Introduction: Presently there are many retro lling materials in the market, nevertheless, little ... more Introduction: Presently there are many retro lling materials in the market, nevertheless, little is known about their toxicity on gingival broblasts. Objective: To assess cytotoxicity of three materials to human gingival fibroblasts and L929 mouse fibroblasts cell line. Material and methods: EndoSequence ® BC RRM TM (ERRM; root repair material), white MTA Angelus ® (MTA) and intermediate restoration material (IRM ®) conditioned media were obtained when materials were freshly mixed, at setting time and after 1, 24 and 72 hours of setting time. Cell morphology was assessed with light microscopy and cell viability was assessed through mitochondrial metabolic activity with 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide (MTT). Statistical analysis was conducted with ANOVA. Results: We found that ERRM material did not exhibit cytotoxic effects on used broblast, nevertheless, MTA and IRM ® respectively exhibited moderate and severe cytotoxicity, thus indicating the materials were not fully harmless. Conclusion: Bioceramic cements like ERRM could be considered the most compatible retro lling-materials.

Research paper thumbnail of Regression of Human Papillomavirus Intraepithelial Lesions Is Induced by MVA E2 Therapeutic Vaccine

Human Gene Therapy, 2014

Human papilloma viruses can induce warts, condylomas, and other intraepithelial cervical lesions ... more Human papilloma viruses can induce warts, condylomas, and other intraepithelial cervical lesions that can progress to cancer. Cervical cancer is a serious problem in developing countries because early detection is difficult, and thus proper early treatment is many times missing. In this phase III clinical trial, we evaluated the potential use of MVA E2 recombinant vaccinia virus to treat intraepithelial lesions associated with papillomavirus infection. A total of 1176 female and 180 male patients with intraepithelial lesions were studied. They were injected with 10 7 MVA E2 virus particles directly into their uterus, urethra, vulva, or anus. Patients were monitored by colposcopy and cytology. Immune response was determined by measuring the antibody titer against MVA E2 virus and by analyzing the cytotoxic activity against cancer cells bearing papillomavirus DNA. Papillomavirus was determined by the Hybrid Capture method or by polymerase chain reaction analysis. By histology, 1051 (89.3%) female patients showed complete elimination of lesions after treatment with MVA E2. In 28 (2.4%) female patients, the lesion was reduced to CIN 1. Another 97 (8.3%) female patients presented isolated koilocytes after treatment. In men, all lesions were completely eliminated. All MVA E2-treated patients developed antibodies against the MVA E2 vaccine and generated a specific cytotoxic response against papilloma-transformed cells. Papillomavirus DNA was not detected after treatment in 83% of total patients treated. MVA E2 did not generate any apparent side effects. These data suggest that therapeutic vaccination with MVA E2 vaccine is an excellent candidate to stimulate the immune system and generate regression in intraepithelial lesions when applied locally.

Research paper thumbnail of Modification of Proliferation and Apoptosis in Breast Cancer Cells by Exposure of Antioxidant Nanoparticles Due to Modulation of the Cellular Redox State Induced by Doxorubicin Exposure

Pharmaceutics, 2021

In this report, we investigated whether the use of chitosan-carrying-glutathione nanoparticles (C... more In this report, we investigated whether the use of chitosan-carrying-glutathione nanoparticles (CH-GSH NPs) can modify proliferation and apoptosis, and reduce cell damage induced by doxorubicin on breast cancer cells. Doxorubicin is a widely used antineoplasic agent for the treatment of various types of cancer. However, it is also a highly toxic drug because it induces oxidative stress. Thus, the use of antioxidant molecules has been considered to reduce the toxicity of doxorubicin. CH-GSH NPs were characterized in size, zeta potential, concentration, and shape. When breast cancer cells were treated with CH-GSH nanoparticles, they were localized in the cellular cytoplasm. Combined doxorubicin exposure with nanoparticles increased intracellular GSH levels. At the same time, decreasing levels of reactive oxygen species and malondialdehyde were observed and modified antioxidant enzyme activity. Levels of the Ki67 protein were evaluated as a marker of cell proliferation and the activity...

Research paper thumbnail of Neutrophils Actively Contribute to Obesity-Associated Inflammation and Pathological Complications

Cells

Obesity is characterized by an increase in body weight associated with an exaggerated enlargement... more Obesity is characterized by an increase in body weight associated with an exaggerated enlargement of the adipose tissue. Obesity has serious negative effects because it is associated with multiple pathological complications such as type 2 diabetes mellitus, cardiovascular diseases, cancer, and COVID-19. Nowadays, 39% of the world population is obese or overweight, making obesity the 21st century epidemic. Obesity is also characterized by a mild, chronic, systemic inflammation. Accumulation of fat in adipose tissue causes stress and malfunction of adipocytes, which then initiate inflammation. Next, adipose tissue is infiltrated by cells of the innate immune system. Recently, it has become evident that neutrophils, the most abundant leukocytes in blood, are the first immune cells infiltrating the adipose tissue. Neutrophils then get activated and release inflammatory factors that recruit macrophages and other immune cells. These immune cells, in turn, perpetuate the inflammation state...

Research paper thumbnail of The Antibody Receptor Fc Gamma Receptor IIIb Induces Calcium Entry via Transient Receptor Potential Melastatin 2 in Human Neutrophils

Frontiers in Immunology, 2021

Human neutrophils express two unique antibody receptors for IgG, the FcγRIIa and the FcγRIIIb. Fc... more Human neutrophils express two unique antibody receptors for IgG, the FcγRIIa and the FcγRIIIb. FcγRIIa contains an immunoreceptor tyrosine-based activation motif (ITAM) sequence within its cytoplasmic tail, which is important for initiating signaling. In contrast, FcγRIIIb is a glycosylphosphatidylinositol (GPI)-linked receptor with no cytoplasmic tail. Although, the initial signaling mechanism for FcγRIIIb remains unknown, it is clear that both receptors are capable of initiating distinct neutrophil cellular functions. For example, FcγRIIa is known to induce an increase in L-selectin expression and efficient phagocytosis, while FcγRIIIb does not promote these responses. In contrast, FcγRIIIb has been reported to induce actin polymerization, activation of β1 integrins, and formation of neutrophils extracellular traps (NET) much more efficiently than FcγRIIa. Another function where these receptors seem to act differently is the increase of cytoplasmic calcium concentration. It has be...

Research paper thumbnail of Editorial: Integrative Approaches to the Molecular Physiology of Inflammation

Frontiers in Physiology, 2018

Research paper thumbnail of Fcγ Receptor Heterogeneity in Leukocyte Functional Responses

Frontiers in Immunology, 2017

FiGURe 1 | Mouse Fcγ receptors (FcγRs). Schematic illustration of mouse receptors for IgG. FcγRs ... more FiGURe 1 | Mouse Fcγ receptors (FcγRs). Schematic illustration of mouse receptors for IgG. FcγRs are shown relative to the cell membrane (yellow line) and together with their respective signaling subunits. γ2, FcR gamma subunit dimer; β2m, beta-2 microglobulin; ITAM, immunoreceptor tyrosine-based activation motif (green rectangle); ITIM, immunoreceptor tyrosine-based inhibition motif (red rectangle); FcRn, neonatal Fc receptor. TRIM21 is a cytosolic receptor. 2 Rosales Each FcγR Activates Distinct Functions

Research paper thumbnail of New Insights on NETosis Induced by Entamoeba histolytica: Dependence on ROS from Amoebas and Extracellular MPO Activity

Antioxidants

NETosis is a neutrophil process involving sequential steps from pathogen detection to the release... more NETosis is a neutrophil process involving sequential steps from pathogen detection to the release of DNA harboring antimicrobial proteins, including the central generation of NADPH oxidase dependent or independent ROS. Previously, we reported that NETosis triggered by Entamoeba histolytica trophozoites is independent of NADPH oxidase activity in neutrophils, but dependent on the viability of the parasites and no ROS source was identified. Here, we explored the possibility that E. histolytica trophozoites serve as the ROS source for NETosis. NET quantitation was performed using SYTOX® Green assay in the presence of selective inhibitors and scavengers. We observed that respiratory burst in neutrophils was inhibited by trophozoites in a dose dependent manner. Mitochondrial ROS was not also necessary, as the mitochondrial scavenger mitoTEMPO did not affect the process. Surprisingly, ROS-deficient amoebas obtained by pre-treatment with pyrocatechol were less likely to induce NETs. Additi...

Research paper thumbnail of Fc receptor functions in host and immune regulation

Revista de investigación clínica

Specific receptors for antibody, named Fc Receptors are proteins found on the surface of leukocyt... more Specific receptors for antibody, named Fc Receptors are proteins found on the surface of leukocytes. Fc receptors contribute to the protective functions of the immune system, by binding to antibodies that are attached to infected cells or invading pathogens. Fc receptor activity stimulates phagocytic or cytotoxic cells to destroy microbes, or infected cells by antibody-mediated phagocytosis or antibody-dependent cell-mediated cytotoxicity. This review describes the main types of Fc receptors and the signal transduction pathways that are initiated by them in various leukocytes, with emphasis on activation of phagocytosis. New findings on the regulatory role of Fc receptors on immune function are also discussed.

Research paper thumbnail of Neutrophils in Cancer: Two Sides of the Same Coin

Journal of Immunology Research, 2015

Neutrophils are the most abundant leukocytes in blood and are considered to be the first line of ... more Neutrophils are the most abundant leukocytes in blood and are considered to be the first line of defense during inflammation and infections. In addition, neutrophils are also found infiltrating many types of tumors. Tumor-associated neutrophils (TANs) have relevant roles in malignant disease. Indeed neutrophils may be potent antitumor effector cells. However, increasing clinical evidence shows TANs correlate with poor prognosis. The tumor microenvironment controls neutrophil recruitment and in turn TANs help tumor progression. Hence, TANs can be beneficial or detrimental to the host. It is the purpose of this review to highlight these two sides of the neutrophil coin in cancer and to describe recent studies that provide some light on the mechanisms for neutrophil recruitment to the tumor, for neutrophils supporting tumor progression, and for neutrophil activation to enhance their antitumor functions.

Research paper thumbnail of Differential Use of Human Neutrophil FcγReceptors for Inducing Neutrophil Extracellular Trap Formation

Journal of Immunology Research, 2016

Neutrophils (PMN) are the most abundant leukocytes in the blood. PMN migrate from the circulation... more Neutrophils (PMN) are the most abundant leukocytes in the blood. PMN migrate from the circulation to sites of infection, where they are responsible for antimicrobial functions. PMN use phagocytosis, degranulation, and formation of neutrophil extracellular traps (NETs) to kill microbes. NETs are fibers composed of chromatin and neutrophil-granule proteins. Several pathogens, including bacteria, fungi, and parasites, and also some pharmacological stimuli such as phorbol 12-myristate 13-acetate (PMA) are efficient inducers of NETs. Antigen-antibody complexes are also capable of inducing NET formation. However the particular Fcγreceptor involved in triggering this function is a matter of controversy. In order to provide some insight into what Fcγreceptor is responsible for NET formation, each of the two human Fcγreceptors was stimulated individually by specific monoclonal antibodies and NET formation was evaluated. FcγRIIa cross-linking did not promote NET formation. Cross-linking other...

Research paper thumbnail of Neutrophils in Cancer: Two Sides of the Same Coin

Neutrophils are the most abundant leukocytes in blood and are considered to be the first line of ... more Neutrophils are the most abundant leukocytes in blood and are considered to be the first line of defense during inflammation and infections. In addition, neutrophils are also found infiltrating many types of tumors. Tumor-associated neutrophils (TANs) have relevant roles in malignant disease. Indeed neutrophils may be potent antitumor effector cells. However, increasing clinical evidence shows TANs correlate with poor prognosis. The tumor microenvironment controls neutrophil recruitment and in turn TANs help tumor progression. Hence, TANs can be beneficial or detrimental to the host. It is the purpose of this review to highlight these two sides of the neutrophil coin in cancer and to describe recent studies that provide some light on the mechanisms for neutrophil recruitment to the tumor, for neutrophils supporting tumor progression, and for neutrophil activation to enhance their antitumor functions.

Research paper thumbnail of Editorial: Phagocytosis: Molecular Mechanisms and Physiological Implications

Frontiers in Immunology, Sep 11, 2020

Research paper thumbnail of Phagocytosis

Reference Module in Biomedical Sciences

Research paper thumbnail of Cellular and Molecular Mechanisms of Insect Immunity

Insect Physiology and Ecology, 2017

Multicellular organisms constantly encounter potentially harmful microorganisms. Although insects... more Multicellular organisms constantly encounter potentially harmful microorganisms. Although insects lack an adaptive immune system, they do have powerful means of fighting infections. Cellular responses involve phagocytosis of bacteria and encapsulation of parasites. In addition, insects can mount a humoral response against pathogens. This is characterized by the secretion of antimicrobial peptides into the hemolymph. Recognition of foreign pathogens involves specific receptors for sensing infection. These include peptidoglycan recognition proteins (PGRPs) and β-glucan recognition proteins (βGRPs). Engagement of these receptors starts signaling pathways that activate the genes that encode antimicrobial peptides. These pathways include the Toll, the Imd, and the JAK-STAT. This chapter describes the innate immunity of insects including both the cellular and humoral responses to bacteria, fungi, and parasites. In addition, recent advances in insect antivirus immune responses are discussed.

Research paper thumbnail of Phosphatidylinositol 3-kinase mediates integrin-dependent NF-κ B and MAPK activation through separate signaling pathways Merit

Research paper thumbnail of Immune Response to the Enteric Parasite Entamoeba histolytica

Physiology

Entamoeba histolytica is a protozoan parasite responsible for amoebiasis, a disease with a high p... more Entamoeba histolytica is a protozoan parasite responsible for amoebiasis, a disease with a high prevalence in developing countries. Establishing an amoebic infection involves interplay between pathogenic factors for invasion and tissue damage, and immune responses for protecting the host. Here, we review the pathogenicity of E. histolytica and summarize the latest knowledge on immune response and immune evasion mechanisms during amoebiasis.

Research paper thumbnail of Fc Receptors: cell activators of antibody functions

Advances in Bioscience and Biotechnology, Apr 1, 2013

At the onset of an infection early defense systems, such as complement, get into action. Speciali... more At the onset of an infection early defense systems, such as complement, get into action. Specialized leukocytes (white blood cells) of the innate immune system, including monocytes, macrophages, and neutrophils also participate as a first line of defense against infections. These early responses are rapid but not very specific and are usually not enough to clear completely many infections. The adaptive immune system is also needed to finish the job against many microorganisms. Antibody molecules, produced during the adaptive immune response, are crucial for preventing recurrent infections. Although, IgG antibodies are essential for controlling infections, these molecules do not directly damage the microorganisms they recognize. Today, it is established that leukocytes of the innate immune system are responsible for the protective effects of these antibodies. IgG molecules bind to their cognate antigens and are in turn recognized by specific receptors (Fcγ receptors) on the membrane of leukocytes. Crosslinking these receptors on the surface of leukocytes leads to activation of several effector cell functions. These effector functions are geared toward the destruction of microbial pathogens and the induction of an inflammatory state that is beneficial during infections. However, in autoimmune diseases, antibodies can direct these effector functions against normal tissues and cause severe tissue damage. In recent years, several factors that can modulate the IgG-FcγR interaction have been elucidated. In this review, we describe the main types of Fcγ receptors, and our current view of how antibody variants interact with these receptors to initiate different cell responses. In addition, new findings on the signaling role of individual Fcγ receptors are also discussed.