Suppressive role of endogenous endothelial monocyte chemoattractant protein-1 on monocyte transendothelial migration...

Monocyte chemoattractant protein-1 (MCP-1, or monocyte chemotactic and activating factor) is thought to play an important role in monocyte infiltration into tissue, but little is known about its effect on monocyte-endothelium interaction. We examined the effect of MCP-1 produced by cytokine-activated endothelial cells (ECs) on monocyte-endothelium adhesion and subsequent transendothelial migration by using a double-chamber vessel model. Unstimulated ECs showed no MCP-1 expression, but exposure to interleukin-1 beta (IL-1 beta, 25 U/mL) induced marked MCP-1 mRNA expression and protein synthesis. When placed in the lower compartment, recombinant human (rh) MCP-1 (100 ng/mL) produced a 1.9-fold and a 2.7-fold increase in adhesion and migration, respectively, compared with a corresponding 51% and 59% decrease when placed in the upper compartment. Migration of monocytes was dependent on a gradient of rh-MCP-1 from the apical to basilar side of the EC layer. Furthermore, a forward gradient of MCP-1 induced adherent cells to increase their subsequent migration, whereas a reverse gradient induced the cells to detach and completely inhibited their subsequent migration. Pretreatment with IL-1 beta for 4 and 24 hours produced a 20% and 63% increase in monocyte migration, respectively. In the presence of anti-MCP-1 antibody, the increase was further enhanced by 52% and 152%, respectively. These results suggest that endogenous endothelial MCP-1, when secreted by IL-1-stimulated ECs, suppresses monocyte migration in the presence of MCP-1 on the basilar side of the EC layer.(ABSTRACT TRUNCATED AT 250 WORDS)