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The Journal of Immunology, 2003, 170: 4325-4334.
Copyright © 2003 by The American Association of Immunologists

L-Selectin or ICAM-1 Deficiency Reduces an Immediate-Type Hypersensitivity Response by Preventing Mast Cell Recruitment in Repeated Elicitation of Contact Hypersensitivity1

Yuka Shimada*, Minoru Hasegawa*, Yuko Kaburagi*, Yasuhito Hamaguchi*, Kazuhiro Komura*, Eriko Saito*, Kazuhiko Takehara*, Douglas A. Steeber{dagger}, Thomas F. Tedder{dagger} and Shinichi Sato2,*

* Department of Dermatology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan; and {dagger} Department of Immunology, Duke University Medical Center, Durham, NC 27710

Repeated Ag exposure results in a shift in the time course of contact hypersensitivity (CH) from a typical delayed-type to an immediate-type response followed by a late phase reaction. Chronic CH responses are clinically relevant to human skin allergic diseases, such as atopic dermatitis, that are usually caused by repeated stimulation with environmental Ags. Chronic inflammatory responses result in part from infiltrating leukocytes. To determine the role of leukocyte adhesion molecules in chronic inflammation, chronic CH responses were assessed in mice lacking L-selectin, ICAM-1, or both adhesion molecules. Following repeated hapten sensitization for 24 days at 2-day intervals, wild-type littermates developed an immediate-type response at 30 min after elicitation, followed by a late phase reaction. By contrast, loss of ICAM-1, L-selectin, or both, eliminated the immediate-type response and inhibited the late phase reaction. Similar results were obtained when wild-type littermates repeatedly exposed to hapten for 22 days were treated with mAbs to L-selectin and/or ICAM-1 before the elicitation on day 24. The lack of an immediate-type response on day 24 paralleled a lack of mast cell accumulation after 30 min of elicitation and decreased serum IgE production. Repeated Ag exposure in wild-type littermates resulted in increased levels of serum L-selectin, a finding also observed in atopic dermatitis patients. The current study demonstrates that L-selectin and ICAM-1 cooperatively regulate the induction of the immediate-type response by mediating mast cell accumulation into inflammatory sites and suggests that L-selectin and ICAM-1 are potential therapeutic targets for regulating human allergic reactions.




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