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

Abstract

roll and adhere in venules exposed to ischemia-reperfusion (I/R). This platelet-endothelial adhesion may influence leukocyte trafficking because platelet depletion decreases I/Rinduced leukocyte emigration. The objectives of this study were 1) to assess the time course of platelet adhesion in the small bowel after I/R and 2) to determine the roles of endothelial and/or platelet P-selectin and P-selectin glycoprotein ligand-1 (PSGL-1) in this adhesion. The adhesion of fluorescently labeled platelets was monitored by intravital microscopy in postcapillary venules exposed to 45 min of ischemia and up to 8 h of reperfusion. Peak platelet adhesion was observed at 4 h of reperfusion. To assess the contributions of platelet and endothelial cell P-selectin, platelets from Pselectin-deficient and wild-type mice were infused into wildtype and P-selectin-deficient mice, respectively. Platelets deficient in P-selectin exhibited low levels of adhesion comparable to that in sham-treated animals. In the absence of endothelial P-selectin, platelet adhesion was reduced by 65%. Treatment with a blocking antibody against PSGL-1 reduced adhesion by 57%. These results indicate that I/R induces a time-dependent platelet-endothelial adhesion response in postcapillary venules via a mechanism that involves PSGL-1 and both platelet and endothelial P-selectin, with platelet P-selectin playing a greater role.

Platelet Recruitment to the Inflamed Glomerulus Occurs via an αIIbβ3/GPVI-Dependent Pathway

“…25,29 Conversely, in other models, platelet accumulation within the inflamed microvasculature is facilitated via interaction with adherent leukocytes. 23,24 In the model of glomerulonephritis used in the present study, our findings indicate that both mechanisms are active, and that recruitment of one cell type facilitates the other. Previously we have found that platelet depletion inhibits leukocyte recruitment and glomerular injury.…”

“…Indeed, leukocytes have been shown to promote platelet adhesion in other inflammatory models. 23,24 In mice treated with anti-GBM antibody, which typically have elevated neutrophil counts, treatment with neutrophil-depleting antibody RB6-8C5 Figure 3. Anti-GBM antibody alters the morphology of the glomerular endothelium within ten minutes.…”

“…20 Platelets have also been shown to interact with the inflamed endothelium via both endothelial and platelet P-selectin. [23][24][25][26] However, in the glomerulus, capillary endothelial cells do not express P-selectin. 2,27,28 Moreover, we observed that P-selectin blockade did not abolish platelet recruitment in the inflamed glomerulus, indicating that P-selectin was not involved in this process.…”

Microcirculatory Disturbances in the Pathogenesis of Acute Pancreatitis

“…Some vascular beds (e.g., intestine) exhibit significant basal expression of P-selectin [55], with little basal expression on inactivated circulating platelets. Several studies have addressed the contributions of platelet vs. endothelial cell P-selectin to the platelet adhesion induced by stimuli such as I/R [56,57], [58], endotoxin [59], and TNF- [60]. In I/R models of platelet adhesion, it appears that those models that elicit a rapid adhesion response in both venules and arterioles are entirely www.intechopen.com dependent on endothelial P-selectin [56], while I/R models exhibiting slow, time-dependent platelet adhesion only in venules involve both platelet and endothelial cell P-selectin [57].…”

“…Several studies have addressed the contributions of platelet vs. endothelial cell P-selectin to the platelet adhesion induced by stimuli such as I/R [56,57], [58], endotoxin [59], and TNF- [60]. In I/R models of platelet adhesion, it appears that those models that elicit a rapid adhesion response in both venules and arterioles are entirely www.intechopen.com dependent on endothelial P-selectin [56], while I/R models exhibiting slow, time-dependent platelet adhesion only in venules involve both platelet and endothelial cell P-selectin [57]. A blocking mAb directed against PSGL-1, a ligand for P-selectin that is expressed on leukocytes and platelets [61], is also effective in attenuating the I/R-induced platelet adhesion observed hours after reperfusion, which further supports a role for plateletderived P-selectin [57].…”