Change in ear swelling induced in L-selectin–deficient (A) and wild-type (B) mice by the nonspecific irritant croton oil. Sixteen hours after croton oil application, the combination of blocking anti–P-selectin (P_B) plus anti–E-selectin was able to significantly reduce ear swelling in both strains of animals (P< .001 compared with no antibody). Nonblocking anti–P-selectin (P_NB) in combination with anti–E-selectin had no effect. L-selectin–deficient mice had ear swelling comparable to that of wild-type animals and anti–L-selectin treatment had no effect on ear swelling in +/+ mice. Each treatment group contained ≥5 animals. (C) Neutrophil infiltrate into croton oil-treated ears is blocked by anti–P-plus anti–E-selectin. Sixteen hours after the application of croton oil to ears of wild-type mice, immunohistochemical staining of ear sections with anti–GR-1 was performed. Cells stained brown are positive for the marker (original magnification × 400). Combined anti-endothelial selectin antibodies show a substantial diminution of both GR-1 staining and ear swelling. L-selectin–deficient mice treated in the same manner showed identical staining patterns (data not shown).