PMID- 9013945 OWN - NLM STAT- MEDLINE DCOM- 19970219 LR - 20071114 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 158 IP - 3 DP - 1997 Feb 1 TI - Fc(gamma) receptor cross-linking induces peripheral blood mononuclear cell monocyte chemoattractant protein-1 expression: role of lymphocyte Fc(gamma)RIII. PG - 1078-84 AB - Immune complexes activate cells by cross-linking leukocyte surface Fc(gamma)Rs. Diseases associated with immune complex deposition, such as rheumatoid arthritis, glomerulonephritis, or idiopathic pulmonary fibrosis, are characterized by compartmentalized monocyte infiltration. The factors that recruit monocytes to these compartments are not well characterized; however, monocyte chemoattractant protein-1 (MCP-1) has been found in areas of tissue injury. To account for these observations we hypothesized that PBMC Fc(gamma)R cross-linking may induce MCP-1 synthesis, which stimulates further monocyte recruitment. To test this hypothesis, PBMC were incubated on increasing concentrations of immobilized human IgG, a stimulus for Fc(gamma)R cross-linking. Immunoreactive MCP-1 was produced in a dose-dependent manner (p < 0.0001). MCP-1 was specifically induced by Fc(gamma)R cross-linking, since immobilized F(ab')2 fragments of human IgG did not activate MCP-1 production. This effect was reproduced by directly cross-linking PBMC Fc(gamma)RIII, but not by cross-linking Fc(gamma)RI or Fc(gamma)RII. PBMC-derived MCP-1 stimulated monocyte chemotaxis that was inhibited by a neutralizing anti-MCP-1 Ab. MCP-1 levels correlated with increased PBMC mRNA expression. Interestingly, Fc(gamma)R cross-linking with either immobilized IgG or anti-Fc(gamma)RIII induced more MCP-1 release from PBMC than from autologous monocytes (p = 0.02). Lymphocytes, the main cell type found in PBMC preparations, did not independently produce a significant amount of MCP-1, but when incubated on immobilized IgG or anti-Fc(gamma)RIII secreted a soluble factor(s) that induced monocyte MCP-1 production. These data suggest that cross-linking PBMC Fc(gamma)R induces the production of bioactive MCP-1. This occurs in part at the level of gene transcription and involves a cooperative interaction between monocytes and lymphocytes. FAU - Marsh, C B AU - Marsh CB AD - Division of Pulmonary and Critical Care Medicine, Ohio State University, Columbus 43210, USA. FAU - Wewers, M D AU - Wewers MD FAU - Tan, L C AU - Tan LC FAU - Rovin, B H AU - Rovin BH LA - eng GR - DK46055/DK/NIDDK NIH HHS/United States GR - HL40871/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Chemokine CCL2) RN - 0 (Immunoglobulin G) RN - 0 (Receptors, IgG) SB - IM MH - Cells, Cultured MH - Chemokine CCL2/*biosynthesis MH - Humans MH - Immunoglobulin G/*immunology MH - Lymphocytes/*immunology MH - Monocytes/*metabolism MH - Receptor Aggregation MH - Receptors, IgG/*physiology MH - Signal Transduction EDAT- 1997/02/01 00:00 MHDA- 1997/02/01 00:01 CRDT- 1997/02/01 00:00 PHST- 1997/02/01 00:00 [pubmed] PHST- 1997/02/01 00:01 [medline] PHST- 1997/02/01 00:00 [entrez] PST - ppublish SO - J Immunol. 1997 Feb 1;158(3):1078-84.