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.