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Inhibition of delayed-type contact hypersensitivity in mice deficient in
both E-selectin and P-selectin
ND Staite, JM Justen, LM Sly, AL Beaudet and DC Bullard
Pharmacia and Upjohn Inc, Kalamazoo, MI 49001, USA.
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.
Volume 88,
Issue 8,
pp. 2973-2979,
10/15/1996
Copyright © 1996 by The American Society of Hematology
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