Fibrin induction of ICAM-1 expression in human vascular endothelial cells.
In acute and chronic inflammatory processes, fibrin deposition, and leukocyte accumulation are classic histopathologic hallmarks. Previous studies have shown that fibrin and fibrin degradation products can have biologic effects on vascular endothelial cells and can induce the expression of several endothelial cell-derived factors that may be important in regulating inflammation and tissue repair. We now demonstrate that coculture of human vascular endothelial cells (EC) with fibrin results in the up-regulation of intercellular adhesion molecule-1 (ICAM-1), thus providing a first link between fibrin deposition and adhesion molecule expression, which may lead subsequently to leukocyte accumulation and extravasation. Increased ICAM-1 expression was demonstrated by ELISA, flow cytometry, and functional adhesion assays. EC ICAM-1 expression increased in a time and dose response fashion. Cell surface levels of ICAM-1 induced by fibrin were comparable to, or exceeded, levels induced by IL-1beta. ICAM-1 expression increased beginning at 4 h post-fibrin formation with sustained elevated expression at 48 h. Fibrin-stimulated EC also bound increased numbers of polymorphonuclear neutrophils in cellular adhesion assays. This increase in adhesion could be blocked by Ab to ICAM-1. Inhibition of fibrin polymerization also inhibited the up-regulation of ICAM-1. Culture medium from fibrin-stimulated EC contained elevated levels of soluble ICAM-1. These data suggest that fibrin deposition on vascular EC, in addition to other reported effects on EC metabolism, may also lead to leukocyte accumulation and extravasation through the induction of leukocyte adhesion molecules such as ICAM-1.
Qi
J
J
Division of Rheumatology, University of Connecticut School of Medicine, Farmington 06032, USA.
Kreutzer
D L
DL
Piela-Smith
T H
TH
D002448:Cell Adhesion / Q000187:drug effects; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005337:Fibrin / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000187:drug effects; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D014471:Umbilical Veins
D018799:Intercellular Adhesion Molecule-1; D005337:Fibrin