P-selectin induces the expression of tissue factor on monocytes.

Abstract

P-selectin on activated platelets and stimulated endothelial cells mediat 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. stimulation of these cells by agonists such as thrombin, P-selectin is phosphorylated (26,27) and rapidly translocated to the plasma membrane (23). P-selectin is a lectin that binds to lineage-specific carbohydrates on the surface of monocytes and neutrophils (28)(29)(30). This protein binds to a mucinlike glycoprotein PSGL-1 that must be properly glycosylated to retain functional properties as the P-selectin ligand (31). P-selectin on platelets mediates the accumulation of leukocytes into the growing thrombus during experimental thrombosis in vivo (32). Inhibitory antibodies that block the interaction of P-selectin on platelets with the P-selectin ligand on leukocytes inhibit the uptake of leukocytes into the thrombus and inhibit the magnitude of thrombus formation. These experiments have demonstrated that P-selectin mediates monocyte and neutrophil interaction with activated platelets in vitro and in vivo. The potential exists for stimulation of leukocyte effector function by P-selectin binding. To evaluate this potential, we have examined the ability of P-selectin to upregulate tissue factor expression on monocytes. In the current study, we demonstrate that P-selectin induces the expression of tissue factor on monocytes exposed to P-selectin. Blood clotting is a host defense mechanism that, in parallel with the inflammatory and repair responses, preserves the integrity of the vascular system after tissue injury (1). Platelets, leukocytes, and endothelial cells are among the cellular components critical for this process. The plasma blood clotting proteins participate in a molecular cascade in which tissue injury activates blood coagulation, leading to the formation of a fibrin clot (2). The response to vascular injury culminates in the formation of a platelet plug, the deposition of ...

Cell‐derived microparticles in synovial fluid from inflamed arthritic joints support coagulation exclusively via a factor VII–dependent mechanism

“…Leukocyte-derived microparticles trigger endothelial cells to produce interleukin-6 (39,40). P-selectin, which is present on platelet-derived microparticles, triggers monocytes to express not only tissue factor, but also chemokines (41,42). Platelet-derived microparticles transport arachidonic acid to endothelial cells and induce the expression of cyclooxygenase 2 and the increased production of prostacyclin (43), enhance the interaction between monocytes and endothelial cells (44), and enhance leukocyte aggregation and their accumulation on the endothelium (45).…”

Variation in the upstream region of P-Selectin (SELP) is a risk factor for SLE

“…P-Selectin is primarily expressed on the cell membrane of platelets and endothelial cells after cellular activation by molecules such as histamine or thrombin, which cause release of the protein from a-granules (platelets) or Weibel-Palade bodies (endothelial cells). [11][12][13][14] The protein functions as an adhesion molecule for a variety of leukocytes, including neutrophils, monocytes, T cells, eosinophils, basophils, platelets and some malignant cells, 15 thereby bringing to sites of inflammation and into contact with a range of cytokines and chemokines expressed by endothelial cells. There are two receptors for P-Selectin, the major leukocyte receptor, P-selectin glycoprotein ligand 1 (PSGL1), which is the high affinity receptor on both myeloid cells and stimulated T lymphocytes, 16,17 and CD24, which is expressed on a number of cells, including B-lineage cells and T lymphocytes.…”

SELPLG Gene Polymorphisms in Relation to Plasma SELPLG Levels and Coronary Artery Disease

“…P-selectin (CD62P) is an adhesion molecule expressed at the surface of the vascular endothelium which, as a consequence of its role in the tethering and rolling of leukocytes on activated endothelial cells (Celi et al 1994;Frenette et al 1995;Geng et al 1990), is a key determinant of the early phases of atherosclerosis. P-selectin is also expressed on the platelet surface and contributes to the formation of aggregates of leukocytes and activated platelets (Weyrich et al 1996).…”