Chronic inflammatory disease alters adhesion molecule requirements for acute neutrophil emigration in mouse skin.
Mutant mice triply deficient in ICAM-1, E-selectin, and P-selectin did not develop the neutrophilic skin lesions that spontaneously arise in mutants doubly deficient in E-selectin and P-selectin. Thus, ICAM-1 is essential to skin disease resulting from endothelial selectin deficiency. During experimental dermatitis, acute neutrophil emigration was completely prevented in young mice deficient in both selectins (E/P and E/P/I mutants). However, older E/P mutants with spontaneous skin lesions displayed an endothelial selectin-independent pathway for acute neutrophil emigration. In contrast, emigration remained compromised in E/P/I mutants and CD18 mutants regardless of age or lesions. Experimentally induced chronic lesions elicited this pathway 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 to skin disease resulting from endothelial selectin deficiency.
Mizgerd
J P
JP
Physiology Program, Harvard School of Public Health, Boston, MA 02115, USA.
Bullard
D C
DC
Hicks
M J
MJ
Beaudet
A L
AL
Doerschuk
C M
CM
D000375:Aging / Q000235:genetics / Q000276:immunology; D000818:Animals; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002465:Cell Movement / Q000276:immunology*; D002908:Chronic Disease; D003436:Croton Oil / Q000633:toxicity; D003877:Dermatitis, Contact / Q000209:etiology / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D019040:E-Selectin / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D019007:P-Selectin / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D012867:Skin / Q000276:immunology / Q000473:pathology*; D013997:Time Factors
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D019007:P-Selectin; D018799:Intercellular Adhesion Molecule-1; D003436:Croton Oil