P-selectin induces the expression of tissue factor on monocytes.
P-selectin on activated platelets and stimulated endothelial cells mediates cell adhesion with monocytes and neutrophils. Since activated platelets induce tissue factor on mononuclear leukocytes, we examined the effect of P-selectin on the expression of tissue factor activity in monocytes. Purified P-selectin stimulated tissue factor expression on mononuclear leukocytes in a dose-dependent manner. Chinese hamster ovary (CHO) cells expressing P-selectin stimulated tissue factor procoagulant activity in purified monocytes, whereas untransfected CHO cells and CHO cells expressing E-selectin did not. Anti-P-selectin antibodies inhibited the effects of purified P-selectin and CHO cells expressing P-selectin on monocytes. Incubation of CHO cells expressing P-selectin with monocytes leads to the development of tissue factor mRNA in monocytes and to the expression of tissue factor antigen on the monocyte surface. These results indicate that P-selectin upregulates the expression of tissue factor on monocytes as well as mediates the binding of platelets and endothelial cells with monocytes and neutrophils. The binding of P-selectin to monocytes in the area of vascular injury may be a component of a mechanism that initiates thrombosis.
Celi
A
A
Center for Hemostasis and Thrombosis Research, New England Medical Center, Boston, MA 02111.
Pellegrini
G
G
Lorenzet
R
R
De Blasi
A
A
Ready
N
N
Furie
B C
BC
Furie
B
B
D015815:Cell Adhesion Molecules / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D009000:Monocytes / Q000378:metabolism*; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism*
D015815:Cell Adhesion Molecules; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D012333:RNA, Messenger; D013925:Thromboplastin