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 inflammatory processes. Moreover, adherence is known to induce cytokine gene expression, suggesting a possible positive feedback mechanism. Therefore, 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 mediated by secretion of interleukin-1 (IL-1). Using monocyte-EC couples obtained after monocyte adhesion to ECs, and methods of quantitative polymerase chain reaction and immunofluorescence flow cytometry, we showed a biphasic increase of ICAM-1 mRNA content (2 and 16 hours) and a time-dependent increase of cell surface expression of ICAM-1, mainly on ECs, and couple adhesiveness, after monocyte adhesion to ECs. Anti-ICAM-1 monoclonal antibody inhibited 63% of the enhancement of adhesiveness induced on monocyte-EC couples by previous monocyte adhesion, suggesting that monocyte adhesion to ECs induces an increase of couple adhesiveness which is partially dependent on the ICAM-1 pathway. The early ICAM-1 mRNA induction was associated with a fast induction of IL-1 beta 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 recombinant 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 endothelial cells appears to stimulate their own recruitment via induction of ICAM-1 thereby constituting a self-perpetuating positive feedback system.
Combe
C
C
Institut National de la Santé et de la Recherche Médicale, Unité 8 de Cardiologie, Pessac, France.
Duplàa
C
C
Couffinhal
T
T
Moreau
C
C
Bonnet
J
J
D001483:Base Sequence; D002448:Cell Adhesion; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism; D008969:Molecular Sequence Data; D009000:Monocytes / Q000502:physiology*; D015345:Oligonucleotide Probes / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism
D007375:Interleukin-1; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1