Mj. Hickey et al., Molecular mechanisms underlying IL-4-induced leukocyte recruitment in vivo: A critical role for the alpha(4) integrin, J IMMUNOL, 163(6), 1999, pp. 3441-3448
IL-4 is known to induce recruitment of eosinophils and mononuclear leukocyt
es. In vitro this occurs in part by selective expression of VCAM-1, the lig
and for the alpha(4) integrin, The objective of this study was to determine
the molecular mechanisms that underlie IL-4-induced leukocyte recruitment
in vivo. Mice received an intrascrotal injection of IL-4 (100 ng), Twenty-f
our hours later, leukocyte rolling, adhesion, and emigration in cremasteric
postcapillary venules were examined via intravital microscopy, and express
ion of VCAM-1 and P- and E-selectin was quantitated using a radiolabeled mA
b technique. IL-4 increased VCAM-1 expression, but P-selectin and E-selecti
n remained at constitutive levels. IL-4 induced significant increases in le
ukocyte adhesion and emigration, with 50% of the emigrated cells being eosi
nophils and the remainder being mononuclear leukocytes, Leukocyte rolling i
n IL-4-treated mice was >95% inhibitable using an anti-P-selectin Ab. Howev
er, IL-4-induced leukocyte recruitment was unaltered in mice treated chroni
cally with P-selectin Ab or mice deficient in either P-selectin or P- and E
-selectin, suggesting that the residual rolling supported all of the IL-4-i
nduced recruitment. In IL-4-treated mice following P-selectin blockade, tet
hering and rolling were not dependent on L-selectin, but were abolished by
alpha(4) integrin blockade. These findings show that the alpha(4) integrin
can initiate leukocyte-endothelial cell interactions in the absence of sele
ctins under shear conditions in vivo, and that the absence of selectins doe
s not affect recruitment of eosinophils and mononuclear cells to IL-4-treat
ed tissue.