Da. Steeber et al., Leukocyte entry into sites of inflammation requires overlapping interactions between the L-selectin and ICAM-1 pathways, J IMMUNOL, 163(4), 1999, pp. 2176-2186
Leukocyte interactions with vascular endothelium during inflammation depend
on cascades of adhesion molecule engagement, particularly during selectin-
mediated leukocyte rolling. Leukocyte rolling is also facilitated by member
s of the integrin and Ig families. Specifically, leukocyte rolling velociti
es during inflammation are significantly increased in ICAM-1-deficient mice
, with ICAM-1 expression required for optimal P- and L-selectin-mediated ro
lling. Elimination of ICAM-1 expression in L-selectin-deficient mice signif
icantly reduces leukocyte rolling. Whether disrupted leukocyte rolling in L
-selectin and ICAM-1 double-deficient (L-selectin/ICAM-1(-/-)) mice affects
leukocyte entry into sites of inflammation in vivo was assessed in the cur
rent study by using experimental models of inflammation; thioglycollate-ind
uced peritonitis, chemokine-induced neutrophil migration to the skin, delay
ed-type hypersensitivity responses, rejection of allogeneic skin grafts, an
d septic shock. In many cases, the loss of both L-selectin and ICAM-1 expre
ssion dramatically reduced leukocyte migration into sites of inflammation b
eyond what was observed with loss of either receptor alone. In fact, the ef
fects from loss of both L-selectin and ICAM-1 effectively eliminated multip
le chronic inflammatory responses in L-selectin/ICAM-1(-/-) mice. By contra
st, the combined loss of L-selectin and ICAM-1 expression had minimal effec
ts on the generation of Ag-specific T cell responses or humoral immunity. T
hus, members of the selectin and Ig families function synergistically to me
diate optimal leukocyte rolling and entry into tissues, which is essential
for the generation of effective inflammatory responses in vivo.