title: Murine macrophage response from peritoneal cavity requires signals mediated by chemokine receptor CCR-2 during Staphylococcus aureus infection.
abstract: C-C chemokine receptor-2 (CCR-2) is a cognate receptor for monocyte chemotactic protein-1 (MCP-1), and recent studies revealed that MCP-1-CCR-2 signaling is involved in several inflammatory diseases characterized by macrophage infiltration. Currently, there is no study on the involvement of CCR-2 in the killing of S. aureus by macrophages of Swiss albino mice, and its substantial role in host defense against S. aureus infection in murine macrophages is still unclear. Therefore, the present study was aimed to investigate the functional and interactive role of CCR-2 and MCP-1 in regulating peritoneal macrophage responses with respect to acute S. aureus infection. We found that phagocytosis of S. aureus can serve as an important stimulus for MCP-1 production by peritoneal macrophages, which is dependent directly or indirectly on cytokines, reactive oxygen species and nitric oxide. Neutralization of CCR-2 in macrophages leads to increased production of IL-10 and decreased production of IFN-γ and IL-6. In CCR-2 blocked macrophages, pretreatment with specific blocker of NF-κB or p38-MAPK causes elevation in MCP-1 level and subsequent downregulation of CCR-2 itself. We speculate that CCR-2 is involved in S. aureus-induced MCP-1 production via NF-κB or p38-MAPK signaling. We also hypothesized that unnaturally high level of MCP-1 that build up upon CCR-2 neutralization might allow promiscuous binding to one or more other chemokine receptors, a situation that would not occur in CCR-2 non-neutralized condition. This may be the plausible explanation for such observed Th-2 response in CCR-2 blocked macrophages infected with S. aureus in the present study.
authors.affiliation: Immunology Laboratory, Department of Physiology, University Colleges of Science and Technology, University of Calcutta, 92 APC Road, Calcutta, West Bengal, 700009, India.
authors.forename: Ajeya
authors.initials: A
authors.lastname: Nandi
authors.affiliation: Immunology Laboratory, Department of Physiology, University Colleges of Science and Technology, University of Calcutta, 92 APC Road, Calcutta, West Bengal, 700009, India. biswa_dev2@yahoo.com.
authors.forename: Biswadev
authors.initials: B
authors.lastname: Bishayi
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D007113:Immunity, Innate / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D054390:Receptors, CCR2 / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013203:Staphylococcal Infections / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D019138:Antibodies, Blocking; C491768:Ccl2 protein, mouse; C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D016207:Cytokines; D016328:NF-kappa B; D054390:Receptors, CCR2; D048051:p38 Mitogen-Activated Protein Kinases
keywords: C–C chemokine receptor-2; Host defense; Monocyte chemotactic protein-1; S. aureus; Th-2 response