Mutant mice triply deficient in ICAM-1, E-selectin, and P-selectin did not
develop the neutrophilic skin lesions that spontaneously arise in mutants d
oubly deficient in E-selectin and P-selectin. Thus, ICAM-1 is essential to
skin disease resulting from endothelial selectin deficiency. During experim
ental dermatitis, acute neutrophil emigration was completely prevented in y
oung mice deficient in both selectins (E/P and E/P/I mutants). However, old
er E/P mutants with spontaneous skin lesions displayed an endothelial selec
tin-independent pathway for acute neutrophil emigration. Ln contract, emigr
ation remained compromised in E/P/I mutants and CD18 mutants regardless of
age or lesions. Experimentally induced chronic lesions elicited this pathwa
y for acute emigration in young E/P mutants. Thus, an endothelial selectin
independent pathway for acute neutrophil emigration is induced in E/P mice
by chronic inflammation at distant sites, and this pathway may contribute t
o skin disease resulting from endothelial selectin deficiency.