PMID- 9409217 OWN - NLM STAT- MEDLINE DCOM- 19980122 LR - 20190831 IS - 1079-5642 (Print) IS - 1079-5642 (Linking) VI - 17 IP - 11 DP - 1997 Nov TI - Basic fibroblast growth factor (bFGF) regulates the expression of the CC chemokine monocyte chemoattractant protein-1 (MCP-1) in autocrine-activated endothelial cells. PG - 2471-8 AB - The CC chemokine monocyte chemoattractant protein (MCP)-1 is induced by inflammatory cytokines and acts as a potent regulator of monocyte trafficking. Monocytes adhere preferentially to migrating endothelial cells in vitro and to endothelial cells at the migration front in vivo after aortic balloon denudation injury. Based on these findings, we analyzed MCP-1 expression in migrating and resting bovine aortic endothelial (BAE) cells and identified prominently upregulated levels of MCP-1 expression in migrating BAE cells. Stimulation of resting BAE cells with 5 ng/mL bFGF resulted in a fourfold induction of MCP-1 mRNA expression. The time course of bFGF-induced MCP-1 mRNA expression indicated a rapid and direct stimulation of MCP-1 expression that was detectable 30 minutes after stimulation. Levels of basal MCP-1 expression, as well as upregulated levels of MCP-1 in migrating BAE cells, were downregulated by addition of a neutralizing anti-bFGF monoclonal antibody (1.0 microgram/mL). Digestion of conditioned media of resting BAE cells with collagenase led to a dose-dependent induction of MCP-1 expression in resting BAE cells, which was inhibited > 50% by addition of neutralizing anti-bFGF antibody. Confirmation of the Northern blot experiments by ELISA-based quantitation of MCP-1 protein levels identified threefold to sixfold higher levels of MCP-1 in the supernatants of bFGF-stimulated BAE cells than in unstimulated resting BAE cells. Finally, analysis of MCP-1 expression by in situ hybridization carried out on en face preparations of aortas demonstrated that MCP-1 expression is dramatically upregulated in regenerating endothelial cells in vivo after balloon denudation. Though not establishing a direct causal relation between the preferential adhesion of monocytes to migrating endothelial cells, these findings strongly suggest that autocrine-activated endothelial cell-derived MCP-1 may play a critical role in recruiting monocytes. They furthermore support the concept that bFGF acts as an autocrine regulator of endothelial cell activity and may imply an involvement of bFGF as a mediator of inflammatory cell trafficking. FAU - Wempe, F AU - Wempe F AD - Department of Gynecology and Obstetrics, University of Gottingen Medical School, Germany. FAU - Lindner, V AU - Lindner V FAU - Augustin, H G AU - Augustin HG LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Arterioscler Thromb Vasc Biol JT - Arteriosclerosis, thrombosis, and vascular biology JID - 9505803 RN - 0 (Antibodies, Monoclonal) RN - 0 (Chemokine CCL2) RN - 0 (RNA, Messenger) RN - 0 (Tumor Necrosis Factor-alpha) RN - 103107-01-3 (Fibroblast Growth Factor 2) RN - 104781-85-3 (Fibroblast Growth Factor 1) RN - EC 3.4.24.- (Collagenases) SB - IM MH - Angioplasty, Balloon/adverse effects MH - Animals MH - Antibodies, Monoclonal/pharmacology MH - Aorta, Thoracic/cytology/injuries MH - Cattle MH - Cell Adhesion MH - Cell Movement MH - Cells, Cultured MH - Chemokine CCL2/*biosynthesis/genetics MH - Collagenases/pharmacology MH - Endothelium, Vascular/injuries/*metabolism/pathology MH - Fibroblast Growth Factor 1/pharmacology MH - Fibroblast Growth Factor 2/antagonists & inhibitors/*pharmacology/physiology MH - *Gene Expression Regulation MH - In Situ Hybridization MH - Male MH - RNA, Messenger/biosynthesis MH - Rats MH - Rats, Sprague-Dawley MH - Tumor Necrosis Factor-alpha/pharmacology MH - Wound Healing EDAT- 1997/12/31 00:00 MHDA- 1997/12/31 00:01 CRDT- 1997/12/31 00:00 PHST- 1997/12/31 00:00 [pubmed] PHST- 1997/12/31 00:01 [medline] PHST- 1997/12/31 00:00 [entrez] AID - 10.1161/01.atv.17.11.2471 [doi] PST - ppublish SO - Arterioscler Thromb Vasc Biol. 1997 Nov;17(11):2471-8. doi: 10.1161/01.atv.17.11.2471.