PMID- 7561060 OWN - NLM STAT- MEDLINE DCOM- 19951027 LR - 20061115 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 155 IP - 7 DP - 1995 Oct 1 TI - A soluble gradient of endogenous monocyte chemoattractant protein-1 promotes the transendothelial migration of monocytes in vitro. PG - 3610-8 AB - Chemokines secreted by endothelium may promote diapedesis of leukocytes by a gradient-dependent chemotactic mechanism or by stimulating random motility so that leukocytes transmigrate in a gradient-independent manner. Alternatively, chemokines may bind to endothelium and extracellular matrix to stimulate haptotactic migration. We first analyzed the role of the chemokine monocyte chemoattractant protein-1 (MCP-1) in the migration of human monocytes across untreated or IL-1-stimulated HUVEC monolayers cultured on human amnion. Then we further examined whether MCP-1-dependent transmigration occurred through a chemokinetic, chemotactic, or haptotactic mechanism. A neutralizing mAb against MCP-1 inhibited passage of monocytes across untreated or IL-1-stimulated HUVEC by 74 +/- 3% and 45 +/- 4%, respectively. Addition of MCP-1 itself to the apical compartment of unstimulated HUVEC/amnion cultures also reduced the transmigration of monocytes, in this instance by 73 +/- 9%. MCP-1 suppressed diapedesis only when present above the endothelium at a concentration equal to or greater than that endogenously deposited beneath the endothelium, and its inhibitory action could be overcome by addition of more concentrated MCP-1 below the HUVEC cultures. As much as 90% of the MCP-1 secreted into the underlying basement membrane and connective tissue could be washed out of HUVEC/amnion cultures; this procedure decreased transmigration by 69 +/- 4%. These data indicate that MCP-1 promotes transmigration of monocytes, but only when present in a gradient across endothelial monolayers. They further suggest that this gradient is predominantly soluble, rather than haptotactic. FAU - Randolph, G J AU - Randolph GJ AD - Department of Pathology, School of Medicine, State University of New York at Stony Brook 11794, USA. FAU - Furie, M B AU - Furie MB LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Chemokine CCL2) RN - 0 (Culture Media, Conditioned) SB - IM MH - Cell Movement/drug effects MH - Cells, Cultured MH - Chemokine CCL2/metabolism/*pharmacology MH - Culture Media, Conditioned MH - Endothelium, Vascular/cytology/*metabolism MH - Humans MH - Monocytes/*cytology/metabolism EDAT- 1995/10/01 00:00 MHDA- 1995/10/01 00:01 CRDT- 1995/10/01 00:00 PHST- 1995/10/01 00:00 [pubmed] PHST- 1995/10/01 00:01 [medline] PHST- 1995/10/01 00:00 [entrez] PST - ppublish SO - J Immunol. 1995 Oct 1;155(7):3610-8.