Monocyte modulation of endothelial leukocyte adhesion molecules

Leukocyte adhesion to endothelium is dependent on expression of specialized molecules. Several of these molecules are upregulated by cytokines such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). We investigated the effect of medium conditioned by unstimulated (MCM) or stimulated monocytes and of recombinant cytokines on endothelial adhesion receptor expression. IL-1β, TNF-α, and MCM induced E-selectin similarly, whereas MCM induced VCAM-1 and ICAM-1 to a lesser extent than did TNF-α, and MCM induced VCAM-1 only weakly. The addition of pentoxifylline (10 -3 mol/L) to monocytes during MCM preparation blocked TNF-α production but not that of IL-1β or IL-6, and it reduced IL-1ra significantly (p<0.05). When the MCM was devoid of TNF-α or when TNF-α was neutralized with a specific antibody, the action of MCM on E-selectin expression was significantly lower. Anti-IL-1β decreased the activity of MCM on endothelial E-selectin expression by about 50%. The effect of MCM on adhesion molecules was accompanied by an increase in monocyte adhesion. Inhibition of TNF-α production reduced monocyte adhesion slightly but significantly (18%, p<0.05), whereas anti-IL-1β antibody decreased adhesion by 48% (p<0.001). There results show that adherent monocytes released cytokines and antagonists that affect leukocyte adhesion receptors on endothelium differently from recombinant cytokines. E-selectin 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 endothelium by monocyte-released cytokines and inhibitors