MONOCYTE MODULATION OF ENDOTHELIAL-LEUKOCYTE ADHESION MOLECULES

Leukocyte adhesion to endothelium is dependent on expression of specia lized molecules. Several of these molecules are upregulated by cytokin es such as interteukin-1 beta (IL-1 beta) and tumor necrosis factor-al pha (TNF-alpha). We investigated the effect of medium conditioned by u nstimulated (MCM) or stimulated monocytes and of recombinant cytokines on endothelial adhesion receptor expression. IL-1 beta, TNF-alpha, an d MCM induced E-selectin similarly, whereas MCM induced VCAM-1 and ICA M-1 to a lesser extent than did TNF-alpha, and MCM induced VCAM-1 only weakly. The addition of pentoxifylline (10(-3) mol/L) to monocytes du ring MCM preparation blocked TNF-alpha. production but not that of IL- 1 beta or IL-6, and it reduced IL-1ra significantly (p < 0.05). When t he MCM was devoid of TNF-alpha or when TNF-alpha was neutralized with a specific antibody, the action of MCM on E-selectin expression was si gnificantly lower, Anti-IL-1 beta decreased the activity of MCM on end othelial E-selectin expression by about 50%. The effect of MCM on adhe sion molecules was accompanied by an increase in monocyte adhesion. In hibition of TNF-alpha production reduced monocyte adhesion slightly bu t significantly (18%, p < 0.05), whereas anti-IL-1 beta antibody decre ased adhesion by 48% (p< 0.001). These results show that adherent mono cytes released cytokines and antagonists that affect leukocyte adhesio n receptors on endothelium differently from recombinant cytokines. E-s electin expression-and to a lesser extent ICAM expression-is modified, resulting in a modulation of leukocyte adhesion to endothelium. This could correspond to a paracrine regulation of monocyte adhesion to end othelium by monocyte-released cytokines and inhibitors.