PMID- 10225970 OWN - NLM STAT- MEDLINE DCOM- 19990610 LR - 20240109 IS - 0021-9738 (Print) IS - 0021-9738 (Linking) VI - 103 IP - 9 DP - 1999 May TI - Chronic inflammation upregulates chemokine receptors and induces neutrophil migration to monocyte chemoattractant protein-1. PG - 1269-76 AB - Monocyte chemoattractant protein-1 (MCP-1) is a CC chemokine that stimulates monocyte recruitment when injected into tissues of healthy animals. However, the function of this chemokine in models with preexisting inflammation is not known. Therefore, MCP-1 was superfused over the mesentery of naive rats or rats with chronic adjuvant-induced vasculitis. MCP-1 elicited increased leukocyte transendothelial migration in adjuvant-immunized rats compared with naive animals. Surprisingly, histology revealed that neutrophils constituted the majority of leukocytes recruited in adjuvant-immunized animals. In vitro, MCP-1 was also able to induce chemotaxis of neutrophils isolated from adjuvant-immunized rats but not from naive rats. Flow cytometry revealed novel expression of the CC chemokine receptors CCR1 and CCR2 on neutrophils from adjuvant-immunized animals. In naive animals, an antibody against CD18 blocked leukocyte adhesion and emigration in response to MCP-1. In adjuvant-immunized animals, leukocyte adhesion was reduced by antibodies against the alpha4-integrin but not by antibodies against CD18. However, the CD18 antibody did block emigration. To our knowledge, this study is the first to show increased sensitivity to a CC chemokine in a model with preexisting inflammation, and altered leukocyte recruitment profiles in response to MCP-1. It also demonstrates that CD18 is required for chemokine-induced leukocyte transendothelial migration, independent of its known role in mediating firm adhesion. J. Clin. Invest. 103:1269-1276 (1999). FAU - Johnston, B AU - Johnston B AD - Immunology Research Group, Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta T2N 4N1, Canada. FAU - Burns, A R AU - Burns AR FAU - Suematsu, M AU - Suematsu M FAU - Issekutz, T B AU - Issekutz TB FAU - Woodman, R C AU - Woodman RC FAU - Kubes, P AU - Kubes P LA - eng GR - P01 HL042550/HL/NHLBI NIH HHS/United States GR - HL-42550/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 Clin Invest JT - The Journal of clinical investigation JID - 7802877 RN - 0 (Chemokine CCL2) RN - 0 (Receptors, Chemokine) SB - IM MH - Animals MH - Cell Adhesion MH - Cell Movement MH - Chemokine CCL2/*metabolism MH - Chronic Disease MH - Male MH - Neutrophils/cytology/*metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, Chemokine/*metabolism MH - *Up-Regulation MH - Vasculitis/*metabolism PMC - PMC408354 EDAT- 1999/05/04 00:00 MHDA- 1999/05/04 00:01 PMCR- 1999/05/01 CRDT- 1999/05/04 00:00 PHST- 1999/05/04 00:00 [pubmed] PHST- 1999/05/04 00:01 [medline] PHST- 1999/05/04 00:00 [entrez] PHST- 1999/05/01 00:00 [pmc-release] AID - 05208 [pii] AID - 10.1172/JCI5208 [doi] PST - ppublish SO - J Clin Invest. 1999 May;103(9):1269-76. doi: 10.1172/JCI5208.