INDUCTION OF INTERCELLULAR-ADHESION MOLECULE-1 BY MONOCYTE ADHESION TO ENDOTHELIAL-CELLS IN HUMAN CULTURE SYSTEM

Increased monocyte adhesion to the endothelial lining of blood vessels by cytokine-inducible adhesion proteins is a crucial event in inflamm atory processes. Moreover, adherence is known to induce cytokine gene expression, suggesting a possible positive feedback mechanism. Therefo re, we determined whether monocyte adhesion to endothelial cells (ECs) amplifies their adhesion by inducing intercellular adhesion molecule 1 (ICAM-1), and whether such positive feedback mechanism could be medi ated by secretion of interleukin-1 (IL-1). Using monocyte-EC couples o btained after monocyte adhesion to ECs, and methods of quantitative po lymerase chain reaction and immunofluorescence flow cytometry, we show ed a biphasic increase of ICAM-1 mRNA content (2 and 16 hours) and a t ime-dependent increase of cell surface expression of ICAM-1, mainly on ECs, and couple adhesiveness, after monocyte adhesion to ECs. Anti-IC AM-1 monoclonal antibody inhibited 63% of the enhancement of adhesiven ess induced on monocyte-EC couples by previous monocyte adhesion, sugg esting that monocyte adhesion to ECs induces an increase of couple adh esiveness which is partially dependent on the ICAM-1 pathway. The earl y ICAM-1 mRNA induction was associated with a fast induction of IL-1 b eta mRNA and a 7.7-fold increase in IL-1 beta protein in supernatant. However, 30% of this 2-hour ICAM-1 mRNA peak was abolished by recombin ant soluble human IL-1 receptor, suggesting that the early ICAM-1 over -expression was partially mediated by IL-1 beta, and could be induced directly by adherence. The second ICAM-1 mRNA peak was accompanied by a marked increase in IL-1 beta mRNA and protein secretion (2.6 ng/ml). The binding to ICAM-1 did not appear to directly stimulate IL-1 beta synthesis. These results indicate that monocyte adhesion to endothelia l cells appears to stimulate their own recruitment via induction of IC AM-1 thereby constituting a self-perpetuating positive feedback system . (C) 1995 Wiley-Liss, Inc.