INHIBITION OF DELAYED-TYPE CONTACT HYPERSENSITIVITY IN MICE DEFICIENTIN BOTH E-SELECTIN AND P-SELECTIN

Leukocyte rolling and emigration in response to inflammatory stimuli a ppears to involve both E-selectin- and P-selectin-dependent adhesion, which suggests that these molecules have overlapping functions. To cla rify their relative contributions in chronic inflammation, we examined delayed-type contact hypersensitivity (DTH) responses in P-selectin, E-selectin, and E-/P-selectin-deficient mice. Oxazolone-induced increa ses in ear thickness and ear weight were equivalent in wild-type mice and in P-selectin and E-selectin mutants, but were significantly reduc ed in E-/P-selectin mutants. The number and area of microabscesses on the ears of E-/P-deficient mice were decreased by 72% and 93%, and the number of leukocytes invading the subdermal ear tissue was reduced. T cells from E-/P-deficient mice transferred oxazolone reactivity into naive wild-type mice. However, when donor T cells from wild-type mice were transferred into E-/P-selectin-deficient mice, the DTH response w as significantly impaired. These results show that leukocyte recruitme nt into a subacute inflammatory reaction can occur when either P-selec tin or E-selectin is present, but is significantly reduced when both s electins are absent, Both P- and E-selectin are likely to play importa nt roles in the development and maintenance of inflammatory diseases. (C) 1996 by The American Society of Hematology.