Marin Lutz - Academia.edu (original) (raw)
Papers by Marin Lutz
Journal of inflammation (London, England), Jan 31, 2005
Peripheral blood monocytes and monocyte-derived macrophages are key regulatory components in many... more Peripheral blood monocytes and monocyte-derived macrophages are key regulatory components in many chronic inflammatory pathologies of the vasculature including the formation of atherosclerotic lesions. However, the molecular and biochemical events underlying monocyte maturation are not fully understood. We have used freshly isolated human monocytes and the model human monocyte cell line, THP-1, to investigate changes in the expression of a panel of monocyte and macrophage markers during monocyte differentiation. We have examined these changes by RT-PCR and FACS analysis. Furthermore, we cloned the CCR2 promoter and analyzed specific changes in transcriptional activation of CCR2 during monocyte maturation. The CC chemokine receptor 2 (CCR2) is rapidly downregulated as monocytes move down the macrophage differentiation pathway while other related chemokine receptors are not. Using a variety of biochemical and transcriptional analyses in the human THP-1 monocyte model system, we show t...
Journal of Clinical Investigation, 2004
Previous reports have identified a circulating pool of CD45 + collagen I + CXCR4 + (CD45 + Col I ... more Previous reports have identified a circulating pool of CD45 + collagen I + CXCR4 + (CD45 + Col I + CXCR4 +) cells, termed fibrocytes, that traffic to areas of fibrosis. No studies have demonstrated that these cells actually contribute to fibrosis, however. Pulmonary fibrosis was originally thought to be mediated solely by resident lung fibroblasts. Here we show that a population of human CD45 + Col I + CXCR4 + circulating fibrocytes migrates in response to CXCL12 and traffics to the lungs in a murine model of bleomycin-induced pulmonary fibrosis. Next, we demonstrated that murine CD45 + Col I + CXCR4 + fibrocytes also traffic to the lungs in response to a bleomycin challenge. Maximal intrapulmonary recruitment of CD45 + Col I + CXCR4 + fibrocytes directly correlated with increased collagen deposition in the lungs. Treatment of bleomycin-exposed animals with specific neutralizing anti-CXCL12 Ab's inhibited intrapulmonary recruitment of CD45 + Col I + CXCR4 + circulating fibrocytes and attenuated lung fibrosis. Thus, our results demonstrate, we believe for the first time, that circulating fibrocytes contribute to the pathogenesis of pulmonary fibrosis. Nonstandard abbreviations used: bronchoalveolar lavage fluid (BAL); collagen I (Col I); idiopathic pulmonary fibrosis (IPF); phycoerythrin (PE); α-smooth muscle actin (α-SMA).
CHEST Journal, 2004
Non-small cell lung cancer is characterized by a specific metastatic pattern. The mechanism for o... more Non-small cell lung cancer is characterized by a specific metastatic pattern. The mechanism for organ-specific metastasis is poorly understood, although recent evidence has suggested that the chemokine stromal derived factor-1 (CXCL12) and its cognate receptor CXCR4 may regulate breast cancer metastasis. We hypothesized that CXCL12/CXCR4 biological axis is important in mediating non-small cell lung cancer metastases. Our results indicate that both non-small cell lung cancer tumor specimens resected from patients and nonsmall cell lung cancer cell lines express CXCR4, but not CXCL12. Non-small cell lung cancer cell lines undergo chemotaxis in response to CXCL12. CXCL12/CXCR4 activation of nonsmall cell lung cancer cell lines showed intracellular calcium mobilization and MAP-kinase activation with enhanced ERK 1/2 phosphorylation without change in either proliferation or apoptosis. Target organs in a murine model that are the preferred destination of human nonsmall cell lung cancer metastases elaborate higher levels of CXCL12 than the primary tumor, and suggest the generation of chemotactic gradients. The administration of specific neutralizing anti-CXCL12 antibodies to SCID mice expressing human non-small cell lung cancer abrogated organ metastases, without affecting primary tumor-derived angiogenesis. These data suggest that the CXCL12/CXCR4 biological axis is involved in regulating the metastasis of non-small cell lung cancer.
American Journal of Respiratory and Critical Care Medicine, 2003
Non-small cell lung cancer is characterized by a specific metastatic to specific organs depending... more Non-small cell lung cancer is characterized by a specific metastatic to specific organs depending on the ability of the organ to pattern. The mechanism for organ-specific metastasis is poorly un-express factor(s) that mediate tumor cell extravasation and derstood, although evidence has suggested that the chemokine recruitment from the vascular to the extravascular tissue comstromal derived factor-1 (CXCL12) and its cognate receptor CXCR4 partment. This pattern of tumor cell metastases may be analomay regulate breast cancer metastasis. We hypothesized that the gous to leukocyte trafficking and tissue extravasation. How-CXCL12-CXCR4 biological axis is important in mediating non-small ever, the specific mechanisms that actually promote organ cell lung cancer metastases. Our results indicate that both non-small metastases have not been fully elucidated. cell lung cancer tumor specimens resected from patients and non-Chemokines are a superfamily of small (8-10 kD) proteins, small cell lung cancer cell lines express CXCR4, but not CXCL12. which play a pivotal role in the regulation of leukocyte traf-Non-small cell lung cancer cell lines undergo chemotaxis in reficking and extravasation through the lumenal surface of ensponse to CXCL12. CXCL12-CXCR4 activation of non-small cell lung dothelial cells into sites of tissue inflammation (7-9). The cancer cell lines showed intracellular calcium mobilization and mitochemokine superfamily includes at least 20 receptors and as gen-activated protein kinase activation with enhanced extracellular many as 40 ligands (7-9). The chemokine ligands can be signal-related kinase-1/2 phosphorylation without change in either separated into four categories depending on whether they proliferation or apoptosis. Target organs in a murine model that express a C, CC, CXC, or CX 3 C amino acid motif in their N are the preferred destination of human non-small cell lung cancer termini. The CXC chemokines bind to a family of G proteinmetastases elaborate higher levels of CXCL12 than does the primary coupled Serpentine (seven transmembrane-spanning) receptumor, and suggest the generation of chemotactic gradients. The tors, which are termed CXC chemokine receptors (CXCRs) administration of specific neutralizing anti-CXCL12 antibodies to (8, 10). Currently six of these receptors have been identified severe combined immunodeficient mice expressing human non-(7, 8, 11-13). CXCL12 (stromal cell-derived factor-1, SDF-1) small cell lung cancer abrogated organ metastases, without affectis a member of the CXC chemokine family, and has been ing primary tumor-derived angiogenesis. These data suggest that found to recruit CD34 ϩ hematopoietic progenitor cells, the CXCL12-CXCR4 biological axis is involved in regulating the megakaryocytes, B cells, and T cells (14). CXCL12 binds metastasis of non-small cell lung cancer. to CXC chemokine receptor 4 (CXCR4) (14). CXCR4 was
American Journal of Psychiatry, 2006
Sibling recurrence risk in autism has been estimated to be approximately 10%. This study investig... more Sibling recurrence risk in autism has been estimated to be approximately 10%. This study investigated subsyndromal autistic impairments among siblings of probands with pervasive developmental disorders. The authors used the Social Responsiveness Scale to obtain quantitative assessments of autistic social impairment in three groups of proband-sibling pairs: 1) autistic children from multiple-incidence families and their closest in age nonautistic brothers (N=49 pairs); 2) children with any pervasive developmental disorder, including autism, and their closest-in-age brothers (N=100 pairs), and 3) children with psychopathology unrelated to autism and their closest-in-age brothers (N=45 pairs). Sibling Social Responsiveness Scale scores were continuously distributed and substantially elevated for both the autistic and pervasive developmental disorder groups. Highest scores (i.e., greatest impairment) were seen among siblings of autistic probands from multiple-incidence families, followed by siblings of probands with any pervasive developmental disorder, then siblings of probands with psychopathology unrelated to autism. Taken together with previous findings, these results support the notion that genetic susceptibility factors responsible for common, subsyndromal social impairments may be related to the causes of categorically defined pervasive developmental disorders.
Journal of inflammation (London, England), Jan 31, 2005
Peripheral blood monocytes and monocyte-derived macrophages are key regulatory components in many... more Peripheral blood monocytes and monocyte-derived macrophages are key regulatory components in many chronic inflammatory pathologies of the vasculature including the formation of atherosclerotic lesions. However, the molecular and biochemical events underlying monocyte maturation are not fully understood. We have used freshly isolated human monocytes and the model human monocyte cell line, THP-1, to investigate changes in the expression of a panel of monocyte and macrophage markers during monocyte differentiation. We have examined these changes by RT-PCR and FACS analysis. Furthermore, we cloned the CCR2 promoter and analyzed specific changes in transcriptional activation of CCR2 during monocyte maturation. The CC chemokine receptor 2 (CCR2) is rapidly downregulated as monocytes move down the macrophage differentiation pathway while other related chemokine receptors are not. Using a variety of biochemical and transcriptional analyses in the human THP-1 monocyte model system, we show t...
Journal of Clinical Investigation, 2004
Previous reports have identified a circulating pool of CD45 + collagen I + CXCR4 + (CD45 + Col I ... more Previous reports have identified a circulating pool of CD45 + collagen I + CXCR4 + (CD45 + Col I + CXCR4 +) cells, termed fibrocytes, that traffic to areas of fibrosis. No studies have demonstrated that these cells actually contribute to fibrosis, however. Pulmonary fibrosis was originally thought to be mediated solely by resident lung fibroblasts. Here we show that a population of human CD45 + Col I + CXCR4 + circulating fibrocytes migrates in response to CXCL12 and traffics to the lungs in a murine model of bleomycin-induced pulmonary fibrosis. Next, we demonstrated that murine CD45 + Col I + CXCR4 + fibrocytes also traffic to the lungs in response to a bleomycin challenge. Maximal intrapulmonary recruitment of CD45 + Col I + CXCR4 + fibrocytes directly correlated with increased collagen deposition in the lungs. Treatment of bleomycin-exposed animals with specific neutralizing anti-CXCL12 Ab's inhibited intrapulmonary recruitment of CD45 + Col I + CXCR4 + circulating fibrocytes and attenuated lung fibrosis. Thus, our results demonstrate, we believe for the first time, that circulating fibrocytes contribute to the pathogenesis of pulmonary fibrosis. Nonstandard abbreviations used: bronchoalveolar lavage fluid (BAL); collagen I (Col I); idiopathic pulmonary fibrosis (IPF); phycoerythrin (PE); α-smooth muscle actin (α-SMA).
CHEST Journal, 2004
Non-small cell lung cancer is characterized by a specific metastatic pattern. The mechanism for o... more Non-small cell lung cancer is characterized by a specific metastatic pattern. The mechanism for organ-specific metastasis is poorly understood, although recent evidence has suggested that the chemokine stromal derived factor-1 (CXCL12) and its cognate receptor CXCR4 may regulate breast cancer metastasis. We hypothesized that CXCL12/CXCR4 biological axis is important in mediating non-small cell lung cancer metastases. Our results indicate that both non-small cell lung cancer tumor specimens resected from patients and nonsmall cell lung cancer cell lines express CXCR4, but not CXCL12. Non-small cell lung cancer cell lines undergo chemotaxis in response to CXCL12. CXCL12/CXCR4 activation of nonsmall cell lung cancer cell lines showed intracellular calcium mobilization and MAP-kinase activation with enhanced ERK 1/2 phosphorylation without change in either proliferation or apoptosis. Target organs in a murine model that are the preferred destination of human nonsmall cell lung cancer metastases elaborate higher levels of CXCL12 than the primary tumor, and suggest the generation of chemotactic gradients. The administration of specific neutralizing anti-CXCL12 antibodies to SCID mice expressing human non-small cell lung cancer abrogated organ metastases, without affecting primary tumor-derived angiogenesis. These data suggest that the CXCL12/CXCR4 biological axis is involved in regulating the metastasis of non-small cell lung cancer.
American Journal of Respiratory and Critical Care Medicine, 2003
Non-small cell lung cancer is characterized by a specific metastatic to specific organs depending... more Non-small cell lung cancer is characterized by a specific metastatic to specific organs depending on the ability of the organ to pattern. The mechanism for organ-specific metastasis is poorly un-express factor(s) that mediate tumor cell extravasation and derstood, although evidence has suggested that the chemokine recruitment from the vascular to the extravascular tissue comstromal derived factor-1 (CXCL12) and its cognate receptor CXCR4 partment. This pattern of tumor cell metastases may be analomay regulate breast cancer metastasis. We hypothesized that the gous to leukocyte trafficking and tissue extravasation. How-CXCL12-CXCR4 biological axis is important in mediating non-small ever, the specific mechanisms that actually promote organ cell lung cancer metastases. Our results indicate that both non-small metastases have not been fully elucidated. cell lung cancer tumor specimens resected from patients and non-Chemokines are a superfamily of small (8-10 kD) proteins, small cell lung cancer cell lines express CXCR4, but not CXCL12. which play a pivotal role in the regulation of leukocyte traf-Non-small cell lung cancer cell lines undergo chemotaxis in reficking and extravasation through the lumenal surface of ensponse to CXCL12. CXCL12-CXCR4 activation of non-small cell lung dothelial cells into sites of tissue inflammation (7-9). The cancer cell lines showed intracellular calcium mobilization and mitochemokine superfamily includes at least 20 receptors and as gen-activated protein kinase activation with enhanced extracellular many as 40 ligands (7-9). The chemokine ligands can be signal-related kinase-1/2 phosphorylation without change in either separated into four categories depending on whether they proliferation or apoptosis. Target organs in a murine model that express a C, CC, CXC, or CX 3 C amino acid motif in their N are the preferred destination of human non-small cell lung cancer termini. The CXC chemokines bind to a family of G proteinmetastases elaborate higher levels of CXCL12 than does the primary coupled Serpentine (seven transmembrane-spanning) receptumor, and suggest the generation of chemotactic gradients. The tors, which are termed CXC chemokine receptors (CXCRs) administration of specific neutralizing anti-CXCL12 antibodies to (8, 10). Currently six of these receptors have been identified severe combined immunodeficient mice expressing human non-(7, 8, 11-13). CXCL12 (stromal cell-derived factor-1, SDF-1) small cell lung cancer abrogated organ metastases, without affectis a member of the CXC chemokine family, and has been ing primary tumor-derived angiogenesis. These data suggest that found to recruit CD34 ϩ hematopoietic progenitor cells, the CXCL12-CXCR4 biological axis is involved in regulating the megakaryocytes, B cells, and T cells (14). CXCL12 binds metastasis of non-small cell lung cancer. to CXC chemokine receptor 4 (CXCR4) (14). CXCR4 was
American Journal of Psychiatry, 2006
Sibling recurrence risk in autism has been estimated to be approximately 10%. This study investig... more Sibling recurrence risk in autism has been estimated to be approximately 10%. This study investigated subsyndromal autistic impairments among siblings of probands with pervasive developmental disorders. The authors used the Social Responsiveness Scale to obtain quantitative assessments of autistic social impairment in three groups of proband-sibling pairs: 1) autistic children from multiple-incidence families and their closest in age nonautistic brothers (N=49 pairs); 2) children with any pervasive developmental disorder, including autism, and their closest-in-age brothers (N=100 pairs), and 3) children with psychopathology unrelated to autism and their closest-in-age brothers (N=45 pairs). Sibling Social Responsiveness Scale scores were continuously distributed and substantially elevated for both the autistic and pervasive developmental disorder groups. Highest scores (i.e., greatest impairment) were seen among siblings of autistic probands from multiple-incidence families, followed by siblings of probands with any pervasive developmental disorder, then siblings of probands with psychopathology unrelated to autism. Taken together with previous findings, these results support the notion that genetic susceptibility factors responsible for common, subsyndromal social impairments may be related to the causes of categorically defined pervasive developmental disorders.