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Philip M Murphy - One of the best experts on this subject based on the ideXlab platform.
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molecular cloning of leukotactin 1 a novel human Beta Chemokine a chemoattractant for neutrophils monocytes and lymphocytes and a potent agonist at cc Chemokine receptors 1 and 3
Journal of Immunology, 1997Co-Authors: Byung S Youn, Massimo Locati, Shang M Zhang, Doo H Park, James E Pease, Kathleen Antol, Hal E. Broxmeyer, Philip M Murphy, Byoung S KwonAbstract:A new member of human Beta-Chemokine cDNA was isolated and named leukotactin-1 (Lkn-1). Lkn-1, along with murine macrophage inflammatory protein-related protein-1 and -2, defines a subgroup of Beta-Chemokines based on two conserved cysteines in addition to the four others conserved in all Beta-Chemokines. The putative mature Lkn-1 is composed of 92 amino acids with a calculated m.w. of 10,162. The Lkn-1 gene was mapped to human chromosome 17, region q12. Recombinant Lkn-1 was a potent chemoattractant for neutrophils, monocytes, and lymphocytes and induced calcium flux in these cells. Lkn-1 specifically induced calcium flux in CCR1- and CCR3-expressing HOS cell lines. Lkn-1 suppressed colony formation by human granulocyte-macrophage, erythroid, and multipotential progenitor cells stimulated by combinations of growth factors. Hence, we have isolated and characterized a human C6 Beta-Chemokine that is a potent agonist at CCR1 and CCR3 and shows broad biologic activities, including leukocyte chemoattraction.
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mapping of the mouse macrophage inflammatory protein 1 alpha receptor gene scya3r and two related mouse Beta Chemokine receptor like genes to chromosome 9
Genomics, 1995Co-Authors: Christine A Kozak, Jiliang Gao, Philip M MurphyAbstract:Abstract Macrophage inflammatory protein-1α (MIP-1α) and RANTES are members of the β Chemokine family of leukocyte chemoattractants. We have previously cloned three mouse genes by cross-hybridization with the human MIP-1α/RANTES receptor gene CMKBR1. One of the mouse genes, Scya3r , encodes a functional MIP-1α receptor. The functions of the other two, Scya3r-rs1 and Scya3r-rs2, are not known. We have now mapped Scya3r, Scya3r-rs1, and Scyca3r-rs2 to chromosome 9, in a region of conserved synteny with the location of CMKBR1. Thus, like Chemokine genes and α Chemokine receptor genes, this group of β Chemokine receptor genes arose by tandem duplication.
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cloning chromosomal localization and rna expression of a human β Chemokine receptor like gene
DNA and Cell Biology, 1995Co-Authors: Christophe Combadiere, Sunil K. Ahuja, Philip M MurphyAbstract:A human cDNA encoding a putative G protein-coupled receptor designated Chemokine Beta receptor-like 1 (CMKBRL1) was isolated from an eosinophilic leukemia library. Its deduced sequence is approximately 40% identical to previously cloned receptors for the Beta Chemokines macrophage inflammatory protein-1 alpha (MIP-1 alpha), RANTES, and monocyte chemoattractant protein-1 (MCP-1), which are chemoattractants for blood leukocytes, and is 83% identical to the product of the orphan rat cDNA RBS 11. Like the MIP-1 alpha/RANTES receptor, CMK-BRL1 is encoded by a small, single-copy gene that maps to chromosome 3p21 and is expressed in leukocytes. However, two screening assays with a broad panel of Chemokines failed to identify its ligand. CMKBRL1 mRNA was detectable by Northern blot hybridization in neutrophils and monocytes, but not eosinophils, and was also found in eight solid organs that were tested with particularly high expression in brain. The RNA distribution of the known Beta Chemokine receptors was overlapping but distinct from that of CMKBRL1. MIP-1 alpha/RANTES receptor mRNA was detectable in neutrophils, monocytes, eosinophils, and in all eight solid organs tested, with particularly high expression in placenta, lung, and liver. MCP-1 receptor mRNA was found in monocytes, lung, liver, and pancreas. These results suggest that the ligand for the putative CMKBRL1 receptor is a Beta Chemokine that targets both neutrophils and monocytes. Moreover, the RNA distributions suggest that CMKBRL1, the MIP-1 alpha/RANTES receptor, and the MCP-1 receptor may have both overlapping and distinct biological roles.
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Molecular piracy of mammalian interleukin-8 receptor type B by herpesvirus saimiri.
Journal of Biological Chemistry, 1993Co-Authors: Sunil K. Ahuja, Philip M MurphyAbstract:Abstract Viruses are known to acquire and modify the genes of their hosts to attain a survival advantage in the host environment. Herpesvirus saimiri (HVS) is a T-lymphotropic virus that causes fatal lymphoproliferative diseases in several non-human primates. The gene ECRF3 of HVS was most likely acquired from a primate host. ECRF3 encodes a putative seven-transmembrane-domain receptor that is remotely related (approximately 30% amino acid identity) to the known mammalian alpha and Beta Chemokine receptors, namely interleukin-8 receptor (IL8R) types A and B and the MIP-1 alpha/RANTES receptor, respectively. Chemokines regulate the trafficking, activation, and, in some cases, proliferation of myeloid and lymphoid cell types. We now show that ECRF3 encodes a functional receptor for the alpha Chemokines IL-8, GRO/melanoma growth stimulatory activity (MGSA), and NAP-2 but not for Beta Chemokines, a specificity identical to that of IL8RB. Paradoxically, IL8RA shares 77% amino acid identity with IL8RB but is not a receptor for GRO/MGSA or NAP-2. This is the first functional characterization of a viral seven-transmembrane-domain receptor. It suggests a novel role for alpha Chemokines in the pathogenesis of HVS infection by transmembrane signaling via the product of ECRF3.
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structure and functional expression of the human macrophage inflammatory protein 1 alpha rantes receptor
Journal of Experimental Medicine, 1993Co-Authors: Douglas B Kuhns, H L Tiffany, David H Mcdermott, Uta Francke, Xu Li, Philip M MurphyAbstract:The Chemokine Beta family is comprised of at least six distinct cytokines that regulate trafficking of phagocytes and lymphocytes in mammalian species; at least one of these, macrophage inflammatory protein 1 alpha (MIP-1 alpha), also regulates the growth of hematopoietic stem cells. We now show that MIP-1 alpha and the related Beta Chemokine, RANTES, induce transient alterations in intracellular Ca2+ concentration in polymorphonuclear leukocytes that can be reciprocally and specifically desensitized, suggesting a common receptor. Moreover, we have now cloned both the cDNA and the gene for this receptor, functionally expressed the receptor in Xenopus oocytes, and mapped the gene to human chromosome 3p21. Transcripts for the receptor were found in mature and immature myeloid cells as well as B cells. The receptor is a member of the G protein-coupled receptor superfamily. It has approximately 33% amino acid identity with receptors for the alpha Chemokine, interleukin 8, and may be the human homologue of the product of US28, an open reading frame of human cytomegalovirus.
Martin E. Dorf - One of the best experts on this subject based on the ideXlab platform.
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identification of a new mouse Beta Chemokine thymus derived chemotactic agent 4 with activity on t lymphocytes and mesangial cells
Journal of Immunology, 1997Co-Authors: Shigeyuki Tanabe, Yi Luo, Elizabeth J Quackenbush, Michael A Berman, Lisa A Collinsracie, Christina R Reilly, Kenneth Jacobs, Martin E. DorfAbstract:Thymus-derived chemotactic agent 4 (TCA4), a new member of the Beta-Chemokine family, was cloned from a mouse thymic cDNA library. High levels of TCA4 mRNA are expressed in thymus; lower levels of message are found in spleen, heart, and kidney. Anti-TCA4 antibodies were used to localize sites of TCA4 expression within lymphoid tissues. In the thymus, UEA-1+ medullary epithelial cells, some endothelial cells, and additional undefined stromal elements were stained with anti-TCA4. TCA4 was also expressed as a meshlike network in splenic white pulp and in the medullary region of the lymph nodes. In addition, some lymph node and splenic blood vessels stained with anti-TCA4 antibodies. Rel B NFkappaB-deficient mice lack a transcription factor required for the generation of dendritic cells and the development of an organized thymic medulla. Rel B-deficient animals express very low levels of TCA4 in the thymus and little or no TCA4 in the periphery. At subnanomolar concentrations, TCA4 is a chemoattractant of mature T cells; the potential role of this novel Chemokine in facilitating normal lymphocyte traffic is discussed. TCA4 is also a chemoattractant of cultured mesangial cells. Neutralizing anti-TCA4 mAb was used to demonstrate the specificity of TCA4-mediated cell migration. Finally, competitive binding studies with a SV40-transformed mouse mesangial cell line demonstrated that other murine Beta-Chemokines (monocyte chemotactic protein-1, macrophage inflammatory protein-1alpha, macrophage inflammatory protein-1Beta, and thymus-derived chemotactic agent 3) do not compete for TCA4 binding.
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Beta Chemokine tca3 binds to and activates rat vascular smooth muscle cells
Journal of Immunology, 1996Co-Authors: Yi Luo, Patricia A Damore, Martin E. DorfAbstract:The present study compares the activity of TCA3 with other Beta-Chemokines (macrophage inflammatory protein (MIP)-1 alpha, MIP-1 Beta, and monocyte chemoattractant protein (MCP)-1) on rat vascular smooth muscle cells. TCA3, MIP-1 alpha, and MCP-1 (but not MIP-1 Beta) treatment stimulates chemotaxis of vascular smooth muscle cells. TCA3-mediated chemotactic responses are sensitive to treatment with pertussis toxin, suggesting that G alpha-i proteins are involved in TCA3 signaling of smooth muscle. In addition, TCA3, MIP-1 alpha, and MCP-1 increase vascular smooth muscle cell adhesiveness to type III collagen. In contrast, stimulation with TCA3, but not other Beta-Chemokines, induces proliferation of vascular smooth muscle cells. TCA3 receptors were identified on rat vascular smooth muscle cells by direct binding of radiolabeled ligand. TCA3 binds to this receptor with high affinity (3 nM). Rat vascular smooth muscle cells display approximately 75,000 binding sites/cell. Competitive inhibition studies indicated that murine MIP-1 alpha, murine MCP-1, and human RANTES are weak partial competitors of TCA3 binding, demonstrating the existence of a unique receptor for TCA3. Murine MIP-1 Beta, which fails to stimulate any biologic functions in vascular smooth muscle cells, also does not inhibit TCA3 binding. The combined data demonstrate that TCA3 and other Beta-Chemokines can modulate vascular smooth muscle cell function.
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Beta Chemokine tca3 binds to mesangial cells and induces adhesion chemotaxis and proliferation
Journal of Immunology, 1996Co-Authors: Yi Luo, Martin E. DorfAbstract:Specific receptors for the Beta-Chemokine TCA3 have been identified on mouse monocyte/macrophage cell lines and on mouse mesangial cells. Using Scatchard plot analysis with 125I-labeled TCA3, a single high-affinity receptor (3-4 nM) was identified. Cells of the monocyte lineage express 1,400 to 8,600 TCA3 binding sites, while mesangial cells display 40,000 to 49,000 sites/cell. Competitive inhibition studies indicated that the TCA3 receptor is unique, although MCP-1, IL-8, and RANTES were weak competitors of TCA3 binding. We also established the functional activity of TCA3 and other Chemokines on primary cultures of mouse mesangial cells. TCA3 treatment induces increased mesangial cell adhesiveness to fibronectin. TCA3 is also a chemoattractant for mesangial cells. In addition, TCA3 treatment stimulates [3H]thymidine uptake by mesangial cells. The combined results indicate that TCA3 and other Chemokines interact with a broader range of target cells than previously considered.
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biologic activities of the Beta Chemokine tca3 on neutrophils and macrophages
Journal of Immunology, 1995Co-Authors: Shamala Devi, J. Laning, Yi Luo, Martin E. DorfAbstract:Previous in vivo and in vitro studies demonstrated that the murine Beta-Chemokine TCA3 is a chemoattractant for monocytes/macrophages and neutrophils. The ability of TCA3 to activate these cell populations is now evaluated. Treatment with 10 to 20 nM rTCA3 induced a respiratory burst with the production of superoxide and hydrogen peroxide in both casein-elicited and unstimulated neutrophil and macrophage populations. In addition, TCA3 treatment induced the production of reactive nitrogen intermediates, whereas stimulation with higher concentrations (100 nM) of TCA3 induced the exocytosis of lysozyme and elastase in the presence of cytochalasin B (7 micrograms/ml). Subnanomolar concentrations (100 pM) of TCA3 also caused integrin-mediated increases of adhesiveness to fibrinogen by neutrophils and macrophages. Increased adhesiveness is the most sensitive assay for TCA3 bioactivity. TCA3 treatment appears to involve signaling through a G-protein-linked receptor as Pertussis toxin abolished the TCA3-mediated increase of adhesiveness and the production of reactive nitrogen intermediates. The dose dependence of the TCA3-mediated activities indicate a coordinated inflammatory response mediated by varying concentrations of TCA3.
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Biologic activities of the murine Beta-Chemokine TCA3.
Journal of immunology (Baltimore Md. : 1950), 1994Co-Authors: Yi Luo, J. Laning, Shamala Devi, T. J. Schall, J. Mak, Martin E. DorfAbstract:The murine Beta-Chemokine TCA3 was purified to homogeneity. The biologic activities of the purified glycoprotein were evaluated in vivo and in vitro. Mice injected i.p. with 1- to 100-ng purified rTCA3 exhibited a rapid influx of neutrophils and macrophages. Increased numbers of neutrophils and monocytes were observed in peripheral blood within 15 min and peak at 45 min. After 45 min neutrophil and macrophage levels were increased in the peritoneal exudate with peak levels occurring at 2 h, followed by a subsequent decline by 24 h. Inflammatory responses were induced in a dose-dependent fashion. The in vivo inflammatory responses were mirrored by the pattern of TCA3-induced chemotaxis in vitro. Neutrophils and macrophages responded to similar concentrations of TCA3 (3 x 10(-9) to 10(-8) M). Lymph node cells responded to other Chemokines but did not migrate to TCA3. We also demonstrated that rTCA3 stimulates a transient increase in cytoplasmic free calcium in monocytic cells through a PTX-sensitive pathway. Cross-desensitization studies indicate that TCA3 acts independently of other Beta-Chemokines (MIP-1 alpha and RANTES) and the alpha-Chemokine IL-8. Furthermore, TCA3 does not induce a Ca2 lux in cells transfected with cDNA for the C-C CKR-1 Chemokine receptor, supporting the conclusion that there are distinct receptors for TCA3.
Yi Luo - One of the best experts on this subject based on the ideXlab platform.
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identification of a new mouse Beta Chemokine thymus derived chemotactic agent 4 with activity on t lymphocytes and mesangial cells
Journal of Immunology, 1997Co-Authors: Shigeyuki Tanabe, Yi Luo, Elizabeth J Quackenbush, Michael A Berman, Lisa A Collinsracie, Christina R Reilly, Kenneth Jacobs, Martin E. DorfAbstract:Thymus-derived chemotactic agent 4 (TCA4), a new member of the Beta-Chemokine family, was cloned from a mouse thymic cDNA library. High levels of TCA4 mRNA are expressed in thymus; lower levels of message are found in spleen, heart, and kidney. Anti-TCA4 antibodies were used to localize sites of TCA4 expression within lymphoid tissues. In the thymus, UEA-1+ medullary epithelial cells, some endothelial cells, and additional undefined stromal elements were stained with anti-TCA4. TCA4 was also expressed as a meshlike network in splenic white pulp and in the medullary region of the lymph nodes. In addition, some lymph node and splenic blood vessels stained with anti-TCA4 antibodies. Rel B NFkappaB-deficient mice lack a transcription factor required for the generation of dendritic cells and the development of an organized thymic medulla. Rel B-deficient animals express very low levels of TCA4 in the thymus and little or no TCA4 in the periphery. At subnanomolar concentrations, TCA4 is a chemoattractant of mature T cells; the potential role of this novel Chemokine in facilitating normal lymphocyte traffic is discussed. TCA4 is also a chemoattractant of cultured mesangial cells. Neutralizing anti-TCA4 mAb was used to demonstrate the specificity of TCA4-mediated cell migration. Finally, competitive binding studies with a SV40-transformed mouse mesangial cell line demonstrated that other murine Beta-Chemokines (monocyte chemotactic protein-1, macrophage inflammatory protein-1alpha, macrophage inflammatory protein-1Beta, and thymus-derived chemotactic agent 3) do not compete for TCA4 binding.
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Beta Chemokine tca3 binds to and activates rat vascular smooth muscle cells
Journal of Immunology, 1996Co-Authors: Yi Luo, Patricia A Damore, Martin E. DorfAbstract:The present study compares the activity of TCA3 with other Beta-Chemokines (macrophage inflammatory protein (MIP)-1 alpha, MIP-1 Beta, and monocyte chemoattractant protein (MCP)-1) on rat vascular smooth muscle cells. TCA3, MIP-1 alpha, and MCP-1 (but not MIP-1 Beta) treatment stimulates chemotaxis of vascular smooth muscle cells. TCA3-mediated chemotactic responses are sensitive to treatment with pertussis toxin, suggesting that G alpha-i proteins are involved in TCA3 signaling of smooth muscle. In addition, TCA3, MIP-1 alpha, and MCP-1 increase vascular smooth muscle cell adhesiveness to type III collagen. In contrast, stimulation with TCA3, but not other Beta-Chemokines, induces proliferation of vascular smooth muscle cells. TCA3 receptors were identified on rat vascular smooth muscle cells by direct binding of radiolabeled ligand. TCA3 binds to this receptor with high affinity (3 nM). Rat vascular smooth muscle cells display approximately 75,000 binding sites/cell. Competitive inhibition studies indicated that murine MIP-1 alpha, murine MCP-1, and human RANTES are weak partial competitors of TCA3 binding, demonstrating the existence of a unique receptor for TCA3. Murine MIP-1 Beta, which fails to stimulate any biologic functions in vascular smooth muscle cells, also does not inhibit TCA3 binding. The combined data demonstrate that TCA3 and other Beta-Chemokines can modulate vascular smooth muscle cell function.
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Beta Chemokine tca3 binds to mesangial cells and induces adhesion chemotaxis and proliferation
Journal of Immunology, 1996Co-Authors: Yi Luo, Martin E. DorfAbstract:Specific receptors for the Beta-Chemokine TCA3 have been identified on mouse monocyte/macrophage cell lines and on mouse mesangial cells. Using Scatchard plot analysis with 125I-labeled TCA3, a single high-affinity receptor (3-4 nM) was identified. Cells of the monocyte lineage express 1,400 to 8,600 TCA3 binding sites, while mesangial cells display 40,000 to 49,000 sites/cell. Competitive inhibition studies indicated that the TCA3 receptor is unique, although MCP-1, IL-8, and RANTES were weak competitors of TCA3 binding. We also established the functional activity of TCA3 and other Chemokines on primary cultures of mouse mesangial cells. TCA3 treatment induces increased mesangial cell adhesiveness to fibronectin. TCA3 is also a chemoattractant for mesangial cells. In addition, TCA3 treatment stimulates [3H]thymidine uptake by mesangial cells. The combined results indicate that TCA3 and other Chemokines interact with a broader range of target cells than previously considered.
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biologic activities of the Beta Chemokine tca3 on neutrophils and macrophages
Journal of Immunology, 1995Co-Authors: Shamala Devi, J. Laning, Yi Luo, Martin E. DorfAbstract:Previous in vivo and in vitro studies demonstrated that the murine Beta-Chemokine TCA3 is a chemoattractant for monocytes/macrophages and neutrophils. The ability of TCA3 to activate these cell populations is now evaluated. Treatment with 10 to 20 nM rTCA3 induced a respiratory burst with the production of superoxide and hydrogen peroxide in both casein-elicited and unstimulated neutrophil and macrophage populations. In addition, TCA3 treatment induced the production of reactive nitrogen intermediates, whereas stimulation with higher concentrations (100 nM) of TCA3 induced the exocytosis of lysozyme and elastase in the presence of cytochalasin B (7 micrograms/ml). Subnanomolar concentrations (100 pM) of TCA3 also caused integrin-mediated increases of adhesiveness to fibrinogen by neutrophils and macrophages. Increased adhesiveness is the most sensitive assay for TCA3 bioactivity. TCA3 treatment appears to involve signaling through a G-protein-linked receptor as Pertussis toxin abolished the TCA3-mediated increase of adhesiveness and the production of reactive nitrogen intermediates. The dose dependence of the TCA3-mediated activities indicate a coordinated inflammatory response mediated by varying concentrations of TCA3.
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Biologic activities of the murine Beta-Chemokine TCA3.
Journal of immunology (Baltimore Md. : 1950), 1994Co-Authors: Yi Luo, J. Laning, Shamala Devi, T. J. Schall, J. Mak, Martin E. DorfAbstract:The murine Beta-Chemokine TCA3 was purified to homogeneity. The biologic activities of the purified glycoprotein were evaluated in vivo and in vitro. Mice injected i.p. with 1- to 100-ng purified rTCA3 exhibited a rapid influx of neutrophils and macrophages. Increased numbers of neutrophils and monocytes were observed in peripheral blood within 15 min and peak at 45 min. After 45 min neutrophil and macrophage levels were increased in the peritoneal exudate with peak levels occurring at 2 h, followed by a subsequent decline by 24 h. Inflammatory responses were induced in a dose-dependent fashion. The in vivo inflammatory responses were mirrored by the pattern of TCA3-induced chemotaxis in vitro. Neutrophils and macrophages responded to similar concentrations of TCA3 (3 x 10(-9) to 10(-8) M). Lymph node cells responded to other Chemokines but did not migrate to TCA3. We also demonstrated that rTCA3 stimulates a transient increase in cytoplasmic free calcium in monocytic cells through a PTX-sensitive pathway. Cross-desensitization studies indicate that TCA3 acts independently of other Beta-Chemokines (MIP-1 alpha and RANTES) and the alpha-Chemokine IL-8. Furthermore, TCA3 does not induce a Ca2 lux in cells transfected with cDNA for the C-C CKR-1 Chemokine receptor, supporting the conclusion that there are distinct receptors for TCA3.
Barbara Sherry - One of the best experts on this subject based on the ideXlab platform.
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induction of the Chemokine Beta peptides mip 1 alpha and mip 1 Beta by lipopolysaccharide is differentially regulated by immunomodulatory cytokines gamma ifn il 10 il 4 and tgf Beta
Molecular Medicine, 1998Co-Authors: Barbara Sherry, Marisol Espinoza, Kirk R Manogue, Anthony CeramiAbstract:The macrophage occupies a central role in the host response to invasion, exerting its control over the developing inflammatory response largely through the elaboration of an assortment of endogenous mediators including many cytokines. The Beta Chemokine peptides, macrophage inflammatory protein [MIP]-1 alpha and MIP-1 Beta, are two such effectors markedly up-regulated in macrophages following exposure to bacterial lipopolysaccharide (LPS). These highly homologous peptides, like the other members of the Beta Chemokine family, exhibit diverse but partially overlapping biological activity profiles, suggesting that the cellular participants and intensity of an inflammatory response may in part be regulated by selective expression of these Chemokines. Studies reported here demonstrate that, in contrast to the "balanced" MIP-1 alpha/MIP-1 Beta Chemokine responses of LPS-stimulated macrophage cultures in vitro, circulating levels of MIP-1 Beta are significantly higher than those of MIP-1 alpha following LPS administration in vivo. Further studies have revealed that several immunomodulatory cytokines known to be up-regulated in vivo as a consequence of exposure to an invasive stimulus (gamma-IFN, IL-10, IL-4, and transforming growth factor [TGF]-Beta) down-regulated the LPS-induced release of MIP-1 alpha by macrophages in vitro, but spared the MIP-1 Beta response. This altered pattern of secretion may explain, at least in part, the high circulating levels of MIP-1 Beta relative to MIP-1 alpha observed in vivo in response to LPS challenge.
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human immunodeficiency virus type 1 infection alters Chemokine Beta peptide expression in human monocytes implications for recruitment of leukocytes into brain and lymph nodes
Proceedings of the National Academy of Sciences of the United States of America, 1996Co-Authors: Helena Schmidtmayerova, Anthony Cerami, Hans S L M Nottet, Gerard J Nuovo, Tobias Raabe, Clinton R Flanagan, Larisa Dubrovsky, Howard E Gendelman, Michael Bukrinsky, Barbara SherryAbstract:Abstract Two Chemokine (chemoattractant cytokines) Beta peptides, macrophage inflammatory proteins 1 alpha and 1 Beta (MIP-1 alpha and MIP-1 Beta), were induced in human monocyte cultures following infection with the human immunodeficiency virus type 1 (HIV-1). Induction depended on productive viral infection: not only did the kinetics of MIP-1 peptide induction closely follow those of viral replication, but monocyte cultures inoculated with heat-inactivated virus or infected in the presence of AZT failed to produce these Chemokine Beta peptides. In addition, HIV infection markedly altered the pattern of Beta Chemokine expression elicited by tumor necrosis factor (TNF), itself a potent proinflammatory cytokine upregulated during the development of AIDS. Reverse transcription (RT)-PCR and RT-in situ PCR studies on brain tissue from patients with AIDS dementia demonstrated elevated MIP-1 alpha and MIP-1 Beta mRNA expression relative to comparable samples from HIV-1-infected patients without dementia. Cells expressing Chemokines in HIV-1-infected brains were identified morphologically as microglia and astrocytes. As MIP-1 alpha and MIP-1 Beta are potent chemoattractants for both monocytes and specific subpopulations of lymphocytes, this dysregulation of Beta Chemokine expression may influence the trafficking of leukocytes during HIV infection. These data, taken together, suggest a mechanism by which HIV-1-infected monocytes might recruit uninfected T cells and monocytes to sites of active viral replication or inflammation, notably the brain and lymph nodes.
Anthony Cerami - One of the best experts on this subject based on the ideXlab platform.
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induction of the Chemokine Beta peptides mip 1 alpha and mip 1 Beta by lipopolysaccharide is differentially regulated by immunomodulatory cytokines gamma ifn il 10 il 4 and tgf Beta
Molecular Medicine, 1998Co-Authors: Barbara Sherry, Marisol Espinoza, Kirk R Manogue, Anthony CeramiAbstract:The macrophage occupies a central role in the host response to invasion, exerting its control over the developing inflammatory response largely through the elaboration of an assortment of endogenous mediators including many cytokines. The Beta Chemokine peptides, macrophage inflammatory protein [MIP]-1 alpha and MIP-1 Beta, are two such effectors markedly up-regulated in macrophages following exposure to bacterial lipopolysaccharide (LPS). These highly homologous peptides, like the other members of the Beta Chemokine family, exhibit diverse but partially overlapping biological activity profiles, suggesting that the cellular participants and intensity of an inflammatory response may in part be regulated by selective expression of these Chemokines. Studies reported here demonstrate that, in contrast to the "balanced" MIP-1 alpha/MIP-1 Beta Chemokine responses of LPS-stimulated macrophage cultures in vitro, circulating levels of MIP-1 Beta are significantly higher than those of MIP-1 alpha following LPS administration in vivo. Further studies have revealed that several immunomodulatory cytokines known to be up-regulated in vivo as a consequence of exposure to an invasive stimulus (gamma-IFN, IL-10, IL-4, and transforming growth factor [TGF]-Beta) down-regulated the LPS-induced release of MIP-1 alpha by macrophages in vitro, but spared the MIP-1 Beta response. This altered pattern of secretion may explain, at least in part, the high circulating levels of MIP-1 Beta relative to MIP-1 alpha observed in vivo in response to LPS challenge.
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human immunodeficiency virus type 1 infection alters Chemokine Beta peptide expression in human monocytes implications for recruitment of leukocytes into brain and lymph nodes
Proceedings of the National Academy of Sciences of the United States of America, 1996Co-Authors: Helena Schmidtmayerova, Anthony Cerami, Hans S L M Nottet, Gerard J Nuovo, Tobias Raabe, Clinton R Flanagan, Larisa Dubrovsky, Howard E Gendelman, Michael Bukrinsky, Barbara SherryAbstract:Abstract Two Chemokine (chemoattractant cytokines) Beta peptides, macrophage inflammatory proteins 1 alpha and 1 Beta (MIP-1 alpha and MIP-1 Beta), were induced in human monocyte cultures following infection with the human immunodeficiency virus type 1 (HIV-1). Induction depended on productive viral infection: not only did the kinetics of MIP-1 peptide induction closely follow those of viral replication, but monocyte cultures inoculated with heat-inactivated virus or infected in the presence of AZT failed to produce these Chemokine Beta peptides. In addition, HIV infection markedly altered the pattern of Beta Chemokine expression elicited by tumor necrosis factor (TNF), itself a potent proinflammatory cytokine upregulated during the development of AIDS. Reverse transcription (RT)-PCR and RT-in situ PCR studies on brain tissue from patients with AIDS dementia demonstrated elevated MIP-1 alpha and MIP-1 Beta mRNA expression relative to comparable samples from HIV-1-infected patients without dementia. Cells expressing Chemokines in HIV-1-infected brains were identified morphologically as microglia and astrocytes. As MIP-1 alpha and MIP-1 Beta are potent chemoattractants for both monocytes and specific subpopulations of lymphocytes, this dysregulation of Beta Chemokine expression may influence the trafficking of leukocytes during HIV infection. These data, taken together, suggest a mechanism by which HIV-1-infected monocytes might recruit uninfected T cells and monocytes to sites of active viral replication or inflammation, notably the brain and lymph nodes.