Inhibition of delayed-type contact hypersensitivity in mice deficient in both E-selectin and P-selectin.
Leukocyte rolling and emigration in response to inflammatory stimuli appears to involve both E-selectin- and P-selectin-dependent adhesion, which suggests that these molecules have overlapping functions. To clarify 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 increases in ear thickness and ear weight were equivalent in wild-type mice and in P-selectin and E-selectin mutants, but were significantly reduced 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 was significantly impaired. These results show that leukocyte recruitment into a subacute inflammatory reaction can occur when either P-selectin or E-selectin is present, but is significantly reduced when both selectins are absent. Both P- and E-selectin are likely to play important roles in the development and maintenance of inflammatory diseases.
Staite
N D
ND
Pharmacia and Upjohn Inc, Kalamazoo, MI 49001, USA.
Justen
J M
JM
Sly
L M
LM
Beaudet
A L
AL
Bullard
D C
DC
D000038:Abscess / Q000209:etiology; D019264:Adoptive Transfer; D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D019040:E-Selectin / Q000235:genetics / Q000502:physiology*; D004487:Edema / Q000209:etiology; D006968:Hypersensitivity, Delayed / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D007958:Leukocyte Count; D051379:Mice; D018345:Mice, Knockout; D010081:Oxazolone / Q000633:toxicity; D019007:P-Selectin / Q000235:genetics / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000637:transplantation
D019040:E-Selectin; D019007:P-Selectin; D010081:Oxazolone