Jordi Esparza - Academia.edu (original) (raw)
Papers by Jordi Esparza
Journal of Investigative Medicine, Mar 1, 2004
Journal of Investigative Medicine, Mar 1, 2004
Journal of Investigative Medicine, Mar 1, 2004
The FASEB Journal, Nov 1, 2005
Integrin engagement induces matrix metalloproteinase (MMP) production by lymphocytes, allowing th... more Integrin engagement induces matrix metalloproteinase (MMP) production by lymphocytes, allowing their progression into tissues. Focal adhesion kinase (FAK) is a key component of integrin-mediated signaling pathways regulating cell migration. We explored the role of FAK in integrin-induced gelatinase production by Jurkat T cells. Elevation of FAK expression by transient transfection increased cell invasiveness and gelatinase production and release driven by fibronectin. FAK point mutants revealed that gelatinase release was not dependent on FAK kinase activity but did require Y397, a binding site for Src-type tyrosine kinases. Requirement of Src kinases was further demonstrated by transfection with Src kinase-deficient mutants and treatment with a Src inhibitor. Transfection of truncated forms demonstrated dual functional elements in the FAK molecule. The FRNK fragment decreased gelatinase release, whereas the FAT subfragment enhanced it. FRNK inhibitory signals were transduced through Src-dependent pCAS phosphorylation and subsequent ERK1/2 activation. In contrast, FAT stimulated gelatinase secretion, which was also dependent on Src-kinase activity, was associated with a decreased ERK1/2 phosphorylation. This dual function of FAK in gelatinase secretion is then associated with changes in ERK1/2 activation status, a pathway coordinating cycles of adhesion/release required for cell migration and defines a novel regulatory step in the complex control of MMP function.
Haematologica, Oct 8, 2009
Background Thalidomide and its analogs are effective agents in the treatment of multiple myeloma.... more Background Thalidomide and its analogs are effective agents in the treatment of multiple myeloma. Since gelatinases (matrix metalloproteinases-2 and-9) play a crucial role in tumor progression, we explored the effect of thalidomide on gelatinase production by malignant B lymphoid cell lines. Design and Methods We investigated the effect of therapeutic doses of thalidomide on integrin-mediated production of gelatinases by malignant B lymphoid cell lines by gelatin zymography, western-blot, reverse transcriptase polymerase chain reaction and invasive capacity through Matrigel-coated Boyden chambers. We also explored the effect of thalidomide on the activation status of the main signaling pathways involved in this process. Results Thalidomide strongly inhibited gelatinase production by B-cell lines and primary myeloma cells in response to fibronectin, the most efficient gelatinase inducer identified in lymphoid cells. Thalidomide disrupted integrin-mediated signaling pathways involved in gelatinase induction and release, such as Src and MAP-kinase ERK activation, resulting in decreased cell motility and invasiveness. Unexpectedly, treatment with thalidomide elicited an increase in fibronectin-induced Akt phosphorylation through phosphoinositide 3-kinase-independent pathways since thalidomide decreased fibronectin-induced phosphoinositide 3-kinase phosphorylation and reversed the inhibition of Akt phosphorylation achieved by the phosphoinositide 3-kinase inhibitors wortmannin and LY294002. Conclusions Disruption of integrin-mediated signaling may be an important mechanism through which thalidomide and its analogs impair tumor cell interactions with the microenvironment. The unexpected effects of thalidomide on Akt activation indicate the need for further studies to elucidate whether the interference with Akt downstream effects would synergize with the antitumor activity of thalidomide.
Journal of Investigative Medicine, 2004
Journal of Investigative Medicine, 2004
Tissue Antigens, 1998
We would like to thank Dr. E. Palmer (Basel Institute for Immunology, Switzerland) for critical r... more We would like to thank Dr. E. Palmer (Basel Institute for Immunology, Switzerland) for critical reading of the manuscript and M. Bayo and C. Moreno for secretarial assistance. This work was supported by 'Fondo de lnvestigaciones Sanitarias de la Seguridad Social" (FIS) grants 96/0788 and 96/0789. F. Lozano is recipient of a grant FIS 95/1102.
Angiogenesis, 1999
Premenopausal women have a lower cardiovascular risk and a higher incidence of several autoimmune... more Premenopausal women have a lower cardiovascular risk and a higher incidence of several autoimmune diseases involving blood vessels than men. Although the precise effects of estrogens on the cardiovascular system are largely unknown, recent data suggest that estrogens can exert direct regulatory effects on endothelial cells. In the present study, we show that 17β-estradiol increases human umbilical vein endothelial cell
Arthritis & Rheumatism, 1998
To investigate endothelial cell adhesion molecule expression in vessels from patients with classi... more To investigate endothelial cell adhesion molecule expression in vessels from patients with classic polyarteritis nodosa (PAN). Frozen sections of 21 muscle and 16 nerve samples from 30 patients with biopsy-proven PAN and 12 histologically normal muscle and 2 histologically normal nerve samples from 12 controls were studied immunohistochemically, using specific monoclonal antibodies (MAb) that recognize adhesion molecules. Adhesion molecules identified were intercellular adhesion molecule 1 (ICAM-1), ICAM-2, ICAM-3, vascular cell adhesion molecule 1 (VCAM-1), platelet endothelial cell adhesion molecule 1 (PECAM-1), E-selectin, P-selectin, L-selectin, lymphocyte function-associated antigen 1 (LFA-1), and very late activation antigen 4 (VLA-4). Neutrophils were identified with a MAb recognizing neutrophil elastase. Endothelial cells were identified with the lectin ulex europaeus. In early lesions, expression of PECAM-1, ICAM-1, ICAM-2, and P-selectin was similar to that in control samples, and VCAM-1 and E-selectin were induced in vascular endothelium. In advanced lesions, immunostaining for adhesion molecules diminished or disappeared in luminal endothelium, whereas these molecules were clearly expressed in microvessels within and surrounding inflamed vessels. Staining in endothelia from vessels in a healing stage tended to be negative. A high proportion of infiltrating leukocytes expressed LFA-1 and VLA-4, and only a minority expressed L-selectin. No relationship between the expression pattern of adhesion molecules and clinical features, disease duration, or previous corticosteroid treatment was observed. Endothelial adhesion molecule expression in PAN is a dynamic process that varies according to the histopathologic stage of the vascular lesions. The preferential expression of constitutive and inducible adhesion molecules in microvessels suggests that angiogenesis contributes to the persistence of inflammatory infiltration in PAN.
Annals of the Rheumatic Diseases, 1994
Objectives-To investigate the prevalence and characteristics of antibodies to endothelial cells (... more Objectives-To investigate the prevalence and characteristics of antibodies to endothelial cells (aEC) from large vessel and from microvasculature in a group of patients with Behcet's disease (BD) to determine the relationship of these antibodies with clinical and laboratory features of the disease. Methods-Thirty patients with BD were prospectively and consecutively studied. The aEC were determined by enzymelinked immunosorbent assay (ELISA) using endothelial cells derived from human umbilical vein (large vessel) as well as from retroperitoneal adipose tissue (microvasculature). Results-Fifteen patients (50%) had aEC, either directed to large vessel [8(26%) patients] or microvascular [13(43%) patients] endothelial cells. The percenitage of active patients was significantly higher in the aEC-positive group [12(80%) patients] compared with the aEC-negative group [5(33%) patients] (p < 0-05). Conclusions-Patients with BD have a high prevalence of aEC when microvascular endothelial cells are used in the assay. These antibodies seem to be a marker of disease activity in this condition, previously considered as negative for autoantibodies.
Clinical and experimental immunology, 1996
Interactions between leucocytes and endothelial cells through specific adhesion receptors play an... more Interactions between leucocytes and endothelial cells through specific adhesion receptors play an increasingly recognized crucial role in the development of inflammatory infiltrates in chronic inflammatory diseases. In this study we investigated adhesion molecule expression in muscle biopsies from 18 dermatomyositis, six polymyositis, five inclusion-body myositis patients and from eight normal controls. Immunohistochemical detection of leucocyte integrins LFA-1 and VLA-4, their endothelial counter-receptors intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), and the endothelial cell markers CD31 and von Willebrand factor-related antigen (vWFAg) was performed using specific MoAbs and an alkaline phosphatase anti-alkaline phosphatase technique. ICAM-1 expression was up-regulated and VCAM-1 induced in muscle capillaries of dermatomyositis samples. In both dermatomyositis and polymyositis, endothelial cells from vessels surrounded by inflammatory i...
Journal of Investigative Medicine
Journal of Investigative Medicine
Blood, Jan 15, 1997
Anti-Sia-lb (formerly anti-Gd) cold agglutinins (CAs) recognize sialylated carbohydrates on both ... more Anti-Sia-lb (formerly anti-Gd) cold agglutinins (CAs) recognize sialylated carbohydrates on both adult and neonate red blood cells (RBCs). RBC CA activity inhibition experiments reported here indicate that the domain NeuNAc alpha2-3Gal, as found in sialyllactose, synthetic sialyl(s) Lewis(Le)(x) and sLe(a), sialyllactosamine, sialyl-fucosyllactose, and nonfucosylated sLe(a), constitutes the minimal epitope for these CAs, implicating that these autoantibodies could be able to bind this domain in sLe(x) and sLe(a) and related carbohydrates expressed on nucleated cells and in soluble cancer-related mucins. The following data obtained with the previously characterized monoclonal IgMk anti-Sia-lb CA, GAS, show that this is the case. GAS epitope expression among leukocytes that lack sLe(a) parallels that of sLe(x) determinant as detected by mouse monoclonal antibodies (MoAbs), especially MoAb KM-93. It is also found on epithelial malignant cells bearing both sLe(x) and sLe(a). GAS epitope...
Arthritis and Rheumatism, 1998
Angiogenesis, 1999
Premenopausal women have a lower cardiovascular risk and a higher incidence of several autoimmune... more Premenopausal women have a lower cardiovascular risk and a higher incidence of several autoimmune diseases involving blood vessels than men. Although the precise effects of estrogens on the cardiovascular system are largely unknown, recent data suggest that estrogens can exert direct regulatory effects on endothelial cells. In the present study, we show that 17β-estradiol increases human umbilical vein endothelial cell attachment to the extracellular matrix proteins laminin-1, type IV collagen, type I collagen, and fibronectin. Estradiol enhanced adhesion most significantly to laminin-1 and to fibronectin-derived synthetic peptides containing an RGD sequence. Upon exposure to estradiol, an increase in β1, α5 and α6 integrin mRNA was observed in subconfluent cells which was abrogated by treatment with cycloheximide. This increase was followed by a later enhancement in surface expression of the above integrins. In addition, integrin-mediated signaling was also enhanced by estrogens si...
European journal of …, 1994
Regulated adhesion of T lymphocytes to antigen-presenting cells, endothelial cells and extracellu... more Regulated adhesion of T lymphocytes to antigen-presenting cells, endothelial cells and extracellular matrix proteins is crucial in T lymphocyte activation and migration to the sites of injury. In this study, we show that three monoclonal antibodies (mAb) recognizing different epitopes on ...
…, 2010
Publisher's Disclaimer. E-publishing ahead of print is increasingly important for the rapid disse... more Publisher's Disclaimer. E-publishing ahead of print is increasingly important for the rapid dissemination of science. Haematologica is, therefore, E-publishing PDF files of an early version of manuscripts that have completed a regular peer review and have been accepted for publication. E-publishing of this PDF file has been approved by the authors.
Journal of Investigative Medicine, Mar 1, 2004
Journal of Investigative Medicine, Mar 1, 2004
Journal of Investigative Medicine, Mar 1, 2004
The FASEB Journal, Nov 1, 2005
Integrin engagement induces matrix metalloproteinase (MMP) production by lymphocytes, allowing th... more Integrin engagement induces matrix metalloproteinase (MMP) production by lymphocytes, allowing their progression into tissues. Focal adhesion kinase (FAK) is a key component of integrin-mediated signaling pathways regulating cell migration. We explored the role of FAK in integrin-induced gelatinase production by Jurkat T cells. Elevation of FAK expression by transient transfection increased cell invasiveness and gelatinase production and release driven by fibronectin. FAK point mutants revealed that gelatinase release was not dependent on FAK kinase activity but did require Y397, a binding site for Src-type tyrosine kinases. Requirement of Src kinases was further demonstrated by transfection with Src kinase-deficient mutants and treatment with a Src inhibitor. Transfection of truncated forms demonstrated dual functional elements in the FAK molecule. The FRNK fragment decreased gelatinase release, whereas the FAT subfragment enhanced it. FRNK inhibitory signals were transduced through Src-dependent pCAS phosphorylation and subsequent ERK1/2 activation. In contrast, FAT stimulated gelatinase secretion, which was also dependent on Src-kinase activity, was associated with a decreased ERK1/2 phosphorylation. This dual function of FAK in gelatinase secretion is then associated with changes in ERK1/2 activation status, a pathway coordinating cycles of adhesion/release required for cell migration and defines a novel regulatory step in the complex control of MMP function.
Haematologica, Oct 8, 2009
Background Thalidomide and its analogs are effective agents in the treatment of multiple myeloma.... more Background Thalidomide and its analogs are effective agents in the treatment of multiple myeloma. Since gelatinases (matrix metalloproteinases-2 and-9) play a crucial role in tumor progression, we explored the effect of thalidomide on gelatinase production by malignant B lymphoid cell lines. Design and Methods We investigated the effect of therapeutic doses of thalidomide on integrin-mediated production of gelatinases by malignant B lymphoid cell lines by gelatin zymography, western-blot, reverse transcriptase polymerase chain reaction and invasive capacity through Matrigel-coated Boyden chambers. We also explored the effect of thalidomide on the activation status of the main signaling pathways involved in this process. Results Thalidomide strongly inhibited gelatinase production by B-cell lines and primary myeloma cells in response to fibronectin, the most efficient gelatinase inducer identified in lymphoid cells. Thalidomide disrupted integrin-mediated signaling pathways involved in gelatinase induction and release, such as Src and MAP-kinase ERK activation, resulting in decreased cell motility and invasiveness. Unexpectedly, treatment with thalidomide elicited an increase in fibronectin-induced Akt phosphorylation through phosphoinositide 3-kinase-independent pathways since thalidomide decreased fibronectin-induced phosphoinositide 3-kinase phosphorylation and reversed the inhibition of Akt phosphorylation achieved by the phosphoinositide 3-kinase inhibitors wortmannin and LY294002. Conclusions Disruption of integrin-mediated signaling may be an important mechanism through which thalidomide and its analogs impair tumor cell interactions with the microenvironment. The unexpected effects of thalidomide on Akt activation indicate the need for further studies to elucidate whether the interference with Akt downstream effects would synergize with the antitumor activity of thalidomide.
Journal of Investigative Medicine, 2004
Journal of Investigative Medicine, 2004
Tissue Antigens, 1998
We would like to thank Dr. E. Palmer (Basel Institute for Immunology, Switzerland) for critical r... more We would like to thank Dr. E. Palmer (Basel Institute for Immunology, Switzerland) for critical reading of the manuscript and M. Bayo and C. Moreno for secretarial assistance. This work was supported by 'Fondo de lnvestigaciones Sanitarias de la Seguridad Social" (FIS) grants 96/0788 and 96/0789. F. Lozano is recipient of a grant FIS 95/1102.
Angiogenesis, 1999
Premenopausal women have a lower cardiovascular risk and a higher incidence of several autoimmune... more Premenopausal women have a lower cardiovascular risk and a higher incidence of several autoimmune diseases involving blood vessels than men. Although the precise effects of estrogens on the cardiovascular system are largely unknown, recent data suggest that estrogens can exert direct regulatory effects on endothelial cells. In the present study, we show that 17β-estradiol increases human umbilical vein endothelial cell
Arthritis & Rheumatism, 1998
To investigate endothelial cell adhesion molecule expression in vessels from patients with classi... more To investigate endothelial cell adhesion molecule expression in vessels from patients with classic polyarteritis nodosa (PAN). Frozen sections of 21 muscle and 16 nerve samples from 30 patients with biopsy-proven PAN and 12 histologically normal muscle and 2 histologically normal nerve samples from 12 controls were studied immunohistochemically, using specific monoclonal antibodies (MAb) that recognize adhesion molecules. Adhesion molecules identified were intercellular adhesion molecule 1 (ICAM-1), ICAM-2, ICAM-3, vascular cell adhesion molecule 1 (VCAM-1), platelet endothelial cell adhesion molecule 1 (PECAM-1), E-selectin, P-selectin, L-selectin, lymphocyte function-associated antigen 1 (LFA-1), and very late activation antigen 4 (VLA-4). Neutrophils were identified with a MAb recognizing neutrophil elastase. Endothelial cells were identified with the lectin ulex europaeus. In early lesions, expression of PECAM-1, ICAM-1, ICAM-2, and P-selectin was similar to that in control samples, and VCAM-1 and E-selectin were induced in vascular endothelium. In advanced lesions, immunostaining for adhesion molecules diminished or disappeared in luminal endothelium, whereas these molecules were clearly expressed in microvessels within and surrounding inflamed vessels. Staining in endothelia from vessels in a healing stage tended to be negative. A high proportion of infiltrating leukocytes expressed LFA-1 and VLA-4, and only a minority expressed L-selectin. No relationship between the expression pattern of adhesion molecules and clinical features, disease duration, or previous corticosteroid treatment was observed. Endothelial adhesion molecule expression in PAN is a dynamic process that varies according to the histopathologic stage of the vascular lesions. The preferential expression of constitutive and inducible adhesion molecules in microvessels suggests that angiogenesis contributes to the persistence of inflammatory infiltration in PAN.
Annals of the Rheumatic Diseases, 1994
Objectives-To investigate the prevalence and characteristics of antibodies to endothelial cells (... more Objectives-To investigate the prevalence and characteristics of antibodies to endothelial cells (aEC) from large vessel and from microvasculature in a group of patients with Behcet's disease (BD) to determine the relationship of these antibodies with clinical and laboratory features of the disease. Methods-Thirty patients with BD were prospectively and consecutively studied. The aEC were determined by enzymelinked immunosorbent assay (ELISA) using endothelial cells derived from human umbilical vein (large vessel) as well as from retroperitoneal adipose tissue (microvasculature). Results-Fifteen patients (50%) had aEC, either directed to large vessel [8(26%) patients] or microvascular [13(43%) patients] endothelial cells. The percenitage of active patients was significantly higher in the aEC-positive group [12(80%) patients] compared with the aEC-negative group [5(33%) patients] (p < 0-05). Conclusions-Patients with BD have a high prevalence of aEC when microvascular endothelial cells are used in the assay. These antibodies seem to be a marker of disease activity in this condition, previously considered as negative for autoantibodies.
Clinical and experimental immunology, 1996
Interactions between leucocytes and endothelial cells through specific adhesion receptors play an... more Interactions between leucocytes and endothelial cells through specific adhesion receptors play an increasingly recognized crucial role in the development of inflammatory infiltrates in chronic inflammatory diseases. In this study we investigated adhesion molecule expression in muscle biopsies from 18 dermatomyositis, six polymyositis, five inclusion-body myositis patients and from eight normal controls. Immunohistochemical detection of leucocyte integrins LFA-1 and VLA-4, their endothelial counter-receptors intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), and the endothelial cell markers CD31 and von Willebrand factor-related antigen (vWFAg) was performed using specific MoAbs and an alkaline phosphatase anti-alkaline phosphatase technique. ICAM-1 expression was up-regulated and VCAM-1 induced in muscle capillaries of dermatomyositis samples. In both dermatomyositis and polymyositis, endothelial cells from vessels surrounded by inflammatory i...
Journal of Investigative Medicine
Journal of Investigative Medicine
Blood, Jan 15, 1997
Anti-Sia-lb (formerly anti-Gd) cold agglutinins (CAs) recognize sialylated carbohydrates on both ... more Anti-Sia-lb (formerly anti-Gd) cold agglutinins (CAs) recognize sialylated carbohydrates on both adult and neonate red blood cells (RBCs). RBC CA activity inhibition experiments reported here indicate that the domain NeuNAc alpha2-3Gal, as found in sialyllactose, synthetic sialyl(s) Lewis(Le)(x) and sLe(a), sialyllactosamine, sialyl-fucosyllactose, and nonfucosylated sLe(a), constitutes the minimal epitope for these CAs, implicating that these autoantibodies could be able to bind this domain in sLe(x) and sLe(a) and related carbohydrates expressed on nucleated cells and in soluble cancer-related mucins. The following data obtained with the previously characterized monoclonal IgMk anti-Sia-lb CA, GAS, show that this is the case. GAS epitope expression among leukocytes that lack sLe(a) parallels that of sLe(x) determinant as detected by mouse monoclonal antibodies (MoAbs), especially MoAb KM-93. It is also found on epithelial malignant cells bearing both sLe(x) and sLe(a). GAS epitope...
Arthritis and Rheumatism, 1998
Angiogenesis, 1999
Premenopausal women have a lower cardiovascular risk and a higher incidence of several autoimmune... more Premenopausal women have a lower cardiovascular risk and a higher incidence of several autoimmune diseases involving blood vessels than men. Although the precise effects of estrogens on the cardiovascular system are largely unknown, recent data suggest that estrogens can exert direct regulatory effects on endothelial cells. In the present study, we show that 17β-estradiol increases human umbilical vein endothelial cell attachment to the extracellular matrix proteins laminin-1, type IV collagen, type I collagen, and fibronectin. Estradiol enhanced adhesion most significantly to laminin-1 and to fibronectin-derived synthetic peptides containing an RGD sequence. Upon exposure to estradiol, an increase in β1, α5 and α6 integrin mRNA was observed in subconfluent cells which was abrogated by treatment with cycloheximide. This increase was followed by a later enhancement in surface expression of the above integrins. In addition, integrin-mediated signaling was also enhanced by estrogens si...
European journal of …, 1994
Regulated adhesion of T lymphocytes to antigen-presenting cells, endothelial cells and extracellu... more Regulated adhesion of T lymphocytes to antigen-presenting cells, endothelial cells and extracellular matrix proteins is crucial in T lymphocyte activation and migration to the sites of injury. In this study, we show that three monoclonal antibodies (mAb) recognizing different epitopes on ...
…, 2010
Publisher's Disclaimer. E-publishing ahead of print is increasingly important for the rapid disse... more Publisher's Disclaimer. E-publishing ahead of print is increasingly important for the rapid dissemination of science. Haematologica is, therefore, E-publishing PDF files of an early version of manuscripts that have completed a regular peer review and have been accepted for publication. E-publishing of this PDF file has been approved by the authors.