Tumor necrosis factor alpha (TNFα) increases platelet-endothelium interaction and platelet rolling in vivo in TNFR1-deficient mice. (a) in vivo platelet-endothelium interaction as analyzed by intravital microscopy in the dorsal skinfold chamber was greatly enhanced in TNFR1−/− mice pretreated with TNFα (5 ng/mL, 4 hours) compared with wild-type (WT) or TNFR2−/− mice treated likewise, as indicated by a leftward shift in platelet velocity distribution pattern in the frequency histogram of analyzed platelet velocities. (b) When rolling platelets (defined as platelets with velocity of less than 5% of maximum velocity) were quantified after TNFα treatment, the fraction related to all analyzed platelets was significantly higher in mice lacking TNFR1 compared with WT or TNFR2-deficient animals. (c) Digital records of carboxyfluorescein-labeled platelets in arterioles with increased platelet-endothelium interaction and rolling platelets (arrow). *Significantly different versus WT and TNFR2−/− mice at P <0.01 (n = 3 to 5). plts, platelets; TNFR1, tumor necrosis factor alpha receptor subtype 1; TNFR2, tumor necrosis factor alpha receptor subtype 2.