PECAM-1 negatively regulates GPIb/V/IX signaling in murine platelets

Phospholipase Cγ2 contributes to stable thrombus formation on VWF

“…PLCc2 deficiency affects the rate and extent of murine platelet thrombus formation on VWF under conditions of arterial shear We have recently shown that washed, red blood cell-reconstituted murine platelets can tether to, become activated by, and form thrombi on huVWF under conditions of arterial shear [18], thereby obviating the need for added botrocetin as a conformational modifier. These conditions are similar to those previously employed to examine huVWF/huGPIb interactions [22,23], and likely involve GPIb-mediated activation events that lead to secretion of (1) soluble agonists such as ADP and (2) adhesive proteins such as VWF and fibrinogen that together support thrombus formation in the absence of exogenously added plasma proteins.…”

“…RGDW peptide, which effectively inhibits GPIIb-IIIa-mediated platelet spreading, was used to determine the surface area covered by attached, but not spread, platelets. Since rodent GPIIb-IIIa is relatively less sensitive to inhibition by RGD peptide than is human GPIIb-IIIa (IC 50 ¼ 1.65 versus 0.04 mM, respectively) [19,20], it was used at a concentration of 2 mM, which has previously been shown to inhibit VWF/botrocetin-induced aggregation and spreading of murine platelets [18].…”

“…Platelet thrombus formation on human VWF under flow was studied using a parallel-plate flow chamber as described previously [18]. Briefly, mepacrine-labeled, red blood cell-reconstituted platelets were perfused through the chamber using a constant rate syringe pump at a Fig.…”

“…Adhesion and spreading of washed wild-type (WT) and PLCc2-deficient [5] murine platelets on human VWF (huVWF) was performed essentially as described previously [18]. RGDW peptide, which effectively inhibits GPIIb-IIIa-mediated platelet spreading, was used to determine the surface area covered by attached, but not spread, platelets.…”

The proinflammatory phenotype of PECAM-1-deficient mice results in atherogenic diet-induced steatohepatitis

“…PECAM-1 has been shown in a number of experimental systems to function as an inhibitory receptor that limits agonist-induced activation of blood and vascular cells (47). To date, PECAM-1 engagement or expression has been shown to inhibit T cell (49), B cell (70), mast cell (72), and platelet (25,52,57) reactivity and to inhibit production of proinflammatory cytokines in vivo (9,41,63). PECAM-1 has also been implicated in maintaining vascular integrity in at least four different in vivo models of inflammation, including intradermal injection of histamine (29), autoimmune encephalomyelitis (29), collagen-induced arthritis (63,71), and lipopolysaccharide-induced endotoxemia (9,41).…”