A Key Role for Cc Chemokine Receptor 4 in Lipopolysaccharide-Induced Endotoxic Shock
| Autor: | Christine A. Power, Yolande Chvatchko, Raphaële Buser, Timothy N. C. Wells, Francois Conquet, Sami Alouani, Amanda E. I. Proudfoot, Pierre Juillard, Alexandra Meyer, Arlene J. Hoogewerf |
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| Rok vydání: | 2000 |
| Předmět: |
Lipopolysaccharides
CCR2 Receptors CCR4 T-Lymphocytes Immunology endotoxic shock Biology Mice Th2 Cells Animals Immunology and Allergy CCL17 CXCL11 CCL13 DNA Primers T helper type 2 cells Chemokine CCL22 Mice Knockout Base Sequence Macrophages lipopolysaccharide F4/80 antigen Shock Septic Molecular biology CXCL2 Chemokines CC CC chemokine receptor 4 Original Article Receptors Chemokine CCL27 Chemokine CCL17 CCL25 CC chemokine receptors |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| DOI: | 10.1084/jem.191.10.1755 |
| Popis: | CC chemokine receptor (CCR)4, a high affinity receptor for the CC chemokines thymus and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC), is expressed in the thymus and spleen, and also by peripheral blood T cells, macrophages, platelets, and basophils. Recent studies have shown that CCR4 is the major chemokine receptor expressed by T helper type 2 (Th2) polarized cells. To study the in vivo role of CCR4, we have generated CCR4-deficient (CCR4(-/-)) mice by gene targeting. CCR4(-/-) mice developed normally. Splenocytes and thymocytes isolated from the CCR4(-/-) mice failed to respond to the CCR4 ligands TARC and MDC, as expected, but also surprisingly did not undergo chemotaxis in vitro in response to macrophage inflammatory protein (MIP)-1alpha. The CCR4 deletion had no effect on Th2 differentiation in vitro or in a Th2-dependent model of allergic airway inflammation. However, CCR4(-/-) mice exhibited significantly decreased mortality on administration of high or low dose bacterial lipopolysaccharide (LPS) compared with CCR4(+/+) mice. After high dose LPS treatment, serum levels of tumor necrosis factor alpha, interleukin 1beta, and MIP-1alpha were reduced in CCR4(-/-) mice, and decreased expression of MDC and MIP-2 mRNA was detected in peritoneal exudate cells. Analysis of peritoneal lavage cells from CCR4(-/)- mice by flow cytometry also revealed a significant decrease in the F4/80(+) cell population. This may reflect a defect in the ability of the CCR4(-/-) macrophages to be retained in the peritoneal cavity. Taken together, our data reveal an unexpected role for CCR4 in the inflammatory response leading to LPS-induced lethality. |
| Databáze: | OpenAIRE |
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