ENHANCEMENT OF MONOCYTE PROCOAGULANT ACTIVITY BY ADHESION ON VASCULARSMOOTH-MUSCLE CELLS AND INTERCELLULAR-ADHESION MOLECULE-1-TRANSFECTEDCHINESE-HAMSTER OVARY CELLS

Background-Plaque erosion is a frequent finding in sudden death due to coronary thrombosis. The present study sought to investigate whether monocyte adhesion to human aortic vascular smooth muscle cells (VSMCs) induces procoagulant activity (PCA) and whether this could be mediate d by intercellular adhesion molecule-1 (ICAM-1). Methods and Results-W e incubated mononuclear cells (MNCs) with VSMCs and ICAM-1-transfected Chinese hamster ovary (CHO) cells, investigated monocyte tissue facto r (TF) mRNA expression by Northern blot analysis and TF protein expres sion by ELISA, and measured PCA. Incubation of MNCs with VSMCs for 6 h ours increased PCA from 0.7+/-0.1 to 166.0+/-37.9 mU/10(5) cells (P=0. 007), which could be inhibited in a dose-dependent manner by the addit ion of blocking anti-ICAM-1 monoclonal antibodies. Prestimulation of V SMCs with interleukin-1 beta enhanced surface ICAM-1 expression signif icantly but did not induce PCA in VSMCs. Incubation of MNCs with prest imulated VSMCs led to a further increase in PCA to 239.9+/-27.9 mU/10( 5) cells (P=0.02 compared with incubation with unstimulated VSMCs). In cubation of MNCs with VSMCs enhanced TF mRNA after 2 hours and signifi cantly increased TF protein content after 6 hours. Incubation of purif ied monocytes with ICAM-1-transfected CHO cells increased PCA from 1.2 +/-0.2 to 81.9+/-3.3 mU/10(5) cells (P<0.001 compared with incubation with untransfected CHO cells) after 6 hours. This effect could be inhi bited significantly by the addition of blocking anti-CD18, anti-CD11b, or anti-CD11c monoclonal antibodies. Similar results were obtained fo r MNCs. Conclusions-Monocyte adhesion to VSMCs induces TF nRNA and pro tein expression and monocyte PCA, which is regulated by beta(2)-integr in-mediated monocyte adhesion to ICAM-1 on VSMCs.