title: Phase-dependent roles of E-selectin during chronic contact hypersensitivity responses.
abstract: Chronic contact hypersensitivity (CH) models induced by repeated hapten exposure exhibit chronic dermatitis and immunological abnormalities resembling atopic dermatitis. To assess the contribution of endothelial selectins (P- and E-selectins) to cutaneous chronic inflammation, chronic CH responses were assessed in mice lacking P- or E-selectin. Elicitation with oxazolone on the ears of P-selectin(-/-) mice 7 days after the sensitization induced a typical delayed-type hypersensitivity response similar to that found in wild-type mice. By contrast, a significant increase in ear swelling was observed in E-selectin(-/-) mice 36 to 48 hours after first elicitation. E-selectin(-/-) mice showed augmented P-selectin up-regulation, and administration of anti-P-selectin monoclonal antibody significantly inhibited the enhanced ear response, suggesting that the enhanced ear-swelling response in E-selectin(-/-) mice resulted from compensatory increase in P-selectin expression. In the late phase of chronic CH, acceleration of ear swelling was significantly reduced in both E- and P-selectin(-/-) mice relative to wild-type littermates. Thus, the loss of P- or E-selectin suppressed inflammatory responses during the chronic phase of the chronic models, whereas early-phase inflammatory responses were exacerbated by E-selectin blockade. Collectively, P- and E-selectins cooperatively regulate CH response, although their roles may be different depending on the phase of the reaction.
authors: Department of Dermatology, Kanazawa University Graduate School of Medical Science, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8641, Japan.
authors: Tomoyuki
authors: T
authors: Fujita
authors: Manabu
authors: M
authors: Fujimoto
authors: Takashi
authors: T
authors: Matsushita
authors: Yuka
authors: Y
authors: Shimada
authors: Minoru
authors: M
authors: Hasegawa
authors: Yoshihiro
authors: Y
authors: Kuwano
authors: Fumihide
authors: F
authors: Ogawa
authors: Kazuhiko
authors: K
authors: Takehara
authors: Shinichi
authors: S
authors: Sato
mesh_terms: D000276:Adjuvants, Immunologic / Q000633:toxicity; D000818:Animals; D002908:Chronic Disease; D003876:Dermatitis, Atopic / Q000276:immunology / Q000378:metabolism; D003877:Dermatitis, Contact / Q000276:immunology* / Q000378:metabolism*; D019040:E-Selectin / Q000276:immunology / Q000378:metabolism*; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010081:Oxazolone / Q000633:toxicity; D019007:P-Selectin / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000276:Adjuvants, Immunologic; D019040:E-Selectin; D019007:P-Selectin; D010081:Oxazolone