Gas6 promotes endothelial sequestration of platelets and leukocytes via P-selectin. (A,B) In vivo videomicroscopy of mesenteric venules revealed impaired platelet-EC interactions in Gas6^−/− mice. Compared with WT mice, fewer platelets tethered/rolled (A) and adhered (B) onto the endothelial surface of the venules after single or combined activation of ECs and platelets. The endothelium was selectively activated by topical administration of A23187. Platelets were selectively activated by injection of collagen together with a GPIIb/IIIa antagonist to avoid aggregation (*P < .05 vs WT, N = 10–21). (C) Loss of Gas6 delayed and impaired the sequestration of leukocytes onto the endothelium, activated by topical administration of A23187. P less than .05 versus WT (ANOVA; *P < .05 vs WT per time point, N = 10-16). (D,E) Impaired and delayed sequestration of leukocytes (D) and platelets (E) onto activated endothelium in Gas6^−/− mice can be explained by reduced P-selectin expression as P-selectin inhibition, by systemic infusion of GA, effectively reduced the interactions between circulating cells and the activated endothelium in WT mice but not in Gas6^−/− mice. Data were expressed as percentage of the maximal value in WT mice. P less than .05 versus WT (ANOVA; N = 7-16 for leukocytes; N = 7-10 for platelets). (F) Release of VWF strings was impaired and delayed in Gas6^−/− mice after topical administration of A23187. Data were expressed as percentage of positive vessels per time point (P < .05 vs WT, ANOVA; N = 10-16).