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Blood, Vol. 92 No. 4 (August 15), 1998:
pp. 1259-1267
Thrombin-Activated Human Endothelial Cells Support Monocyte
Adhesion In Vitro Following Expression of Intercellular Adhesion
Molecule-1 (ICAM-1; CD54) and Vascular Cell Adhesion Molecule-1
(VCAM-1; CD106)
Gilles Kaplanski,
Valérie Marin,
Martine Fabrigoule,
Vera Boulay,
Anne-Marie Benoliel,
Pierre Bongrand,
Solange Kaplanski, and
Catherine Farnarier
From the Laboratoire d'Immunologie-INSERM U387, Hôpital
Sainte-Marguerite, Marseille, France.
Thrombin, a central molecule in coagulation, is also involved in
inflammation. Notably, thrombin induces endothelial neutrophil adhesion, P- and E-selectin expression, and chemokine production. We
show here that thrombin induces expression of intercellular adhesion
molecule-1 (ICAM-1; CD54) and vascular cell adhesion molecule-1
(VCAM-1; CD106) on human umbilical vein endothelial cells (HUVECs)
associated with increased adhesion of monocytes. Thrombin increased
mRNA steady-state levels and expression of ICAM-1 over 24 hours.
Thrombin-induced VCAM-1 expression exhibited unusual kinetics, reaching
maximum levels after 6 to 12 hours, but decreasing to near baseline
after 24 hours. Thrombin activity on HUVECs was mediated through
interaction with its specific receptor, because ICAM-1 and VCAM-1
expression were similarly induced by the 14-amino acid thrombin
receptor-activating peptide. Thrombin-induced ICAM-1 and VCAM-1
expression was significantly inhibited by hirudin, but not by
interleukin-1 receptor antagonist or anti-tumor necrosis factor 
monoclonal antibody (MoAb). Thrombin-activated HUVECs significantly
increased greater numbers of adhering THP-1 macrophagic cells,
peripheral blood mononuclear cells, or purified monocytes than
unstimulated HUVECs. This adhesion was inhibited by anti-CD18 and
anti-CD49d MoAb, demonstrating that thrombin-induced ICAM-1 and VCAM-1
were functional. These results show that, in addition to selectins,
thrombin directly induces a cytokine-independent expression of adhesion
molecules of the Ig superfamily on HUVECs that may support firm
leukocyte attachment during inflammation.
© 1998 by The American Society of Hematology.
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