Lymphocytes induce monocyte chemoattractant protein-1 production by renal cells after Fc gamma receptor cross-linking: role of IL-1beta.
Leukocyte recruitment to the kidney in immune complex disease like systemic lupus erythematosus (SLE) is mediated in part by local expression of chemokines such as monocyte chemoattractant protein-1 (MCP-1). Recent studies from this laboratory demonstrated that cross-linking Fc gammaR on lymphocytes causes release of a soluble factor that induces monocyte chemokine production. To explain the induction of renal chemokine expression in immune complex disease, we postulated that this lymphocyte factor stimulates renal parenchymal cell MCP-1 expression. To test this hypothesis, human peripheral blood lymphocytes were incubated on immobilized IgG, a model for immune complex Fc gammaR cross-linking. Supernatants from these lymphocyte cultures significantly increased MCP-1 production by human mesangial, glomerular capillary endothelial, and proximal tubular epithelial cells. Mesangial cells incubated on immobilized IgG or with soluble, preformed immune complexes did not secrete MCP-1 above control levels. Lymphocyte supernatant-induced MCP-1 production appeared to be dependent on the presence of interleukin (IL)-1beta in the supernatant. Removing IL-1beta from the supernatants, antagonizing its activity, or preventing conversion to mature IL-1beta abrogated renal cell MCP-1 expression by the lymphocyte supernatants. These data demonstrate that in response to cross-linking Fc gammaR, lymphocytes induce renal cell MCP-1 expression by secreting IL-1beta. Renal chemokine expression in immune complex disease may thus be triggered as lymphocytes traffic through the kidney and encounter deposited immune complexes.
Department of Internal Medicine and the Heart Lung Research Institute, The Ohio State University School of Medicine and Public Health, USA. rovin.1@osu.edu
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D000936:Antigen-Antibody Complex / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000494:pharmacology; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D007668:Kidney / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism*
D000936:Antigen-Antibody Complex; D018932:Chemokine CCL2; D007074:Immunoglobulin G; D007375:Interleukin-1; D017452:Receptors, IgG