THE ROLES OF L-SELECTIN, BETA-7 INTEGRINS, AND P-SELECTIN IN LEUKOCYTE ROLLING AND ADHESION IN HIGH ENDOTHELIAL VENULES OF PEYERS-PATCHES

Lymphocyte trafficking into Peyer's patches requires beta(7) integrins and L-selectin, Here, we use intravital microscopy to examine leukocy te rolling and adhesion in Peyer's patch high endothelial venules (HEV ) of wild-type, L-selectin-deficient (L-/-), beta(7) integrin-deficien t (beta(7)(-/-)), and beta(7)/L-/- mice. Although the leukocyte rollin g Bur fraction was reduced by 70%, Peyer's patches in L-/- mice were o f normal size and cellularity. In beta(7)(-/-) mice, the rolling flux fraction was normal, but the number of adherent leukocytes in HEV was greatly reduced. The median leukocyte rolling velocity was reduced in L-/- mice and increased in beta(7)/L-/- mice, suggesting that beta(7) integrins and L-selectin mediate rolling in Peyer's patch HEV at diffe rent velocities. beta(7)/L-/- exhibited both a low rolling flux fracti on and low adhesion and had severely reduced Peyer's patch size and ce llularity. The residual rolling in these mice was completely blocked b y a P-selectin mAb, A significant P-selectin component was also detect ed in the other genotypes, Twenty-six percent of B and T lymphocytes i solated from Peyer's patches of wild-type mice expressed functional li gands for P-selectin, and this fraction was increased to 57% in beta(7 )/L-/- mice. Peyer's patch HEV were found to express P-selectin under the conditions of intravital microscopy, but not in situ, Our data sug gest a novel P-selectin dependent mechanism of lymphocyte homing to Pe yer's patches. In situ, beta(7) integrins and L-selectin account for a ll lymphocyte homing to Peyer's patches, but P-selectin-dependent roll ing, as induced by minimal trauma, may support trafficking of effector T lymphocytes to Peyer's patches.