Platelets roll on stimulated endothelium in vivo: an interaction mediated by endothelial P-selectin.

Abstract

P-selectin, found in storage granules ofplatelets and endothelial cells, can be rapidly expressed upon stimulation. Mice lacking this membrane receptor exhibit a severe impairment of leukocyte rolling. We observed that, in addition to leukocytes, platelets were rolling in mesenteric venules of wild-typej mice. To investigate the role of P-selectin in this process, resting or activated platelets from wild-type or P-selectin-deficient mice were fluorescently labeled and transfused into recipients of either genotype. Platelet-endothelial interactions were monitored by intravital microscopy. We observed rolling of either wild-type or P-selectin-deficient resting platelets on wild-type endothelium. Endothelial stimulation with the calcium ionophore A23187 increased the number of platelets rolling 4-fold. Activated P-selectindeficient platelets behaved similarly, whereas activated wildtype platelets bound to leukocytes and were seen rolling together. Platelets of either genotype, resting or activated, interacted minimally with mutant endothelium even after A23187 treatment. The velocity of platelet rolling was 6-to 9-fold greater than that of leukocytes. Our results demonstrate that (i) platelets roll on endothelium in vivo, (ii) this interaction requires endothelial but not platelet P-selectin, and (iii) platelet rolling appears to be independent of platelet activation, indicating constitutive expression of a P-selectin ligand(s) on platelets. We have therefore observed an interesting parallel between platelets and leukocytes in that both of these blood cell types roll on stimulated vessel wall and that this process is dependent on the expression of endothelial P-selectin.Rolling of blood cells along the endothelial surface of venules was first described >150 years ago when leukocytes were shown to adhere to the walls of blood vessels and this interaction increased in inflammation (1, 2). Subsequently, Atherton and Born (3) developed the modern version of intravital microscopy and made the first quantitative observations of leukocyte rolling in the cheek pouch of hamsters and in mouse mesentery. Leukocyte rolling is the initial stage of a multistep process leading to extravasation of white blood cells to sites of inflammation or infection (4, 5). The selectin family has been shown by in vitro experimentation (6) and by intravital microscopy (7-9) to mediate this rolling motion.One member of this family of adhesion molecules, Pselectin, is stored preformed in a granules of platelets (10, 11) and in Weibel-Palade bodies of endothelial cells (12, 13). After stimulated secretion and expression on the cell surface, both platelet and endothelial P-selectin mediate adhesion to leukocytes (14, 15). Beside its role in binding to leukocytes, the biological relevance of platelet P-selectin, a specific marker of platelet activation, is still unknown. In vitro, neutrophils have been shown to roll on P-selectin of immobilized activated platelets (16). Endothelial P-selectin is a key mediator of leukocyte rolling and subseq...

Platelets and platelet adhesion support angiogenesis while preventing excessive hemorrhage

“…Resting platelets interact with endothelium by binding to P-selectin or VWF (50,51). Both proteins can bind to GPIb (51,52).…”

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).…”

Time-dependent platelet-vessel wall interactions induced by intestinal ischemia-reperfusion

“…Intravital microscopy has been used to monitor and quantify the recruitment of platelets in postcapillary venules during acute inflammation, including endotoxemia (2), exposure to tumor necrosis factor-␣ (6) and calcium ionophore (5), and I/R (22,23,26). These studies have revealed that some stimuli elicit a rapid platelet-adhesion response (ionophore) while other stimuli require hours to initiate a significant response (LPS).…”