Activation of both VEGFR1 on neutrophils and VEGFR2 on endothelium is necessary for in vivo VEGF-A-induced neutrophil recruitment. (A-B) Specific knockdown of either VEGFR1 tyrosine kinase (Flt-1 tk^−/− mice) or VEGFR2-TSAd-Src signaling (tsad^−/− mice) inhibited VEGF-A (2 nM)-dependent neutrophil recruitment to the cremaster muscle (n = 4-7 mice per group). The number of (C) adherent and (D) emigrated neutrophils recruited in vivo by the proinflammatory chemokine MIP-2 (CXCL2; 0.5 nM) in the cremaster muscle of both Flt-1 tk^−/− and tsad^−/− mice was similar to that in the cremaster muscle of WT mice (n = 5-6 mice per group). (E-F) VEGF-A-dependent neutrophil recruitment was inhibited in WT mice transplanted with Flt-1 tk^−/− bone marrow whereas neutrophil recruitment to VEGF-A was unaffected in WT mice transplanted with tsad^−/− bone marrow (n = 5-6 mice per group). #P, .05 compared with basal values within the same group; *P < .05 compared with other groups, as indicated.