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).
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 alpha 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.
Kaplanski
G
G
Laboratoire d'Immunologie-INSERM U387, Hôpital Sainte-Marguerite, Marseille, France.
Marin
V
V
Fabrigoule
M
M
Boulay
V
V
Benoliel
A M
AM
Bongrand
P
P
Kaplanski
S
S
Farnarier
C
C
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002448:Cell Adhesion; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006629:Hirudins / Q000494:pharmacology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000502:physiology*; D053590:Interleukin 1 Receptor Antagonist Protein; D007963:Leukocytes, Mononuclear / Q000166:cytology*; D009000:Monocytes / Q000166:cytology*; D010446:Peptide Fragments / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D018179:Receptors, Thrombin / Q000187:drug effects / Q000502:physiology; D012795:Sialoglycoproteins / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology; D014471:Umbilical Veins; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000502:physiology*
D000911:Antibodies, Monoclonal; D006629:Hirudins; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D010446:Peptide Fragments; D012333:RNA, Messenger; D018179:Receptors, Thrombin; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D013917:Thrombin