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4 Integrin1
*
Immunology Research Group, University of Calgary, Calgary, Alberta, Canada; and
Department of Molecular and Cellular Physiology, Louisiana State University Medical Center, Shreveport, LA 71130
IL-4 is known to induce recruitment of eosinophils and mononuclear
leukocytes. In vitro this occurs in part by selective expression of
VCAM-1, the ligand for the 
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-four hours later,
leukocyte rolling, adhesion, and emigration in cremasteric
postcapillary venules were examined via intravital microscopy, and
expression of VCAM-1 and P- and E-selectin was quantitated using a
radiolabeled mAb technique. IL-4 increased VCAM-1 expression, but
P-selectin and E-selectin remained at constitutive levels. IL-4 induced
significant increases in leukocyte adhesion and emigration, with 50%
of the emigrated cells being eosinophils and the remainder being
mononuclear leukocytes. Leukocyte rolling in IL-4-treated mice was
>95% inhibitable using an anti-P-selectin Ab. However,
IL-4-induced leukocyte recruitment was unaltered in mice treated
chronically 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-induced recruitment. In IL-4-treated mice following
P-selectin blockade, tethering and rolling were not dependent on
L-selectin, but were abolished by 4 integrin blockade.
These findings show that the 4 integrin can initiate
leukocyte-endothelial cell interactions in the absence of selectins
under shear conditions in vivo, and that the absence of selectins does
not affect recruitment of eosinophils and mononuclear cells to
IL-4-treated tissue.
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