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Department of Biomedical Engineering, University of Virginia School of Medicine, Charlottesville, VA 22908;
Department of Immunology, Duke University Medical Center, Durham, NC 27710; and
Institute for Genetics, University of Cologne, Cologne, Germany
Lymphocyte trafficking into Peyers patches requires ß7 integrins and L-selectin. Here, we use intravital microscopy to examine leukocyte rolling and adhesion in Peyers patch high endothelial venules (HEV) of wild-type, L-selectin-deficient (L-/-), ß7 integrin-deficient (ß7-/-), and ß7/L-/- mice. Although the leukocyte rolling flux fraction was reduced by 70%, Peyers patches in L-/- mice were of normal size and cellularity. In ß7-/- 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 ß7-/- mice, suggesting that ß7 integrins and L-selectin mediate rolling in Peyers patch HEV at different velocities. ß7/L-/- exhibited both a low rolling flux fraction and low adhesion and had severely reduced Peyers patch size and cellularity. The residual rolling in these mice was completely blocked by a P-selectin mAb. A significant P-selectin component was also detected in the other genotypes. Twenty-six percent of B and T lymphocytes isolated from Peyers patches of wild-type mice expressed functional ligands for P-selectin, and this fraction was increased to 57% in ß7/L-/- mice. Peyers patch HEV were found to express P-selectin under the conditions of intravital microscopy, but not in situ. Our data suggest a novel P-selectin dependent mechanism of lymphocyte homing to Peyers patches. In situ, ß7 integrins and L-selectin account for all lymphocyte homing to Peyers patches, but P-selectin-dependent rolling, as induced by minimal trauma, may support trafficking of effector T lymphocytes to Peyers patches.
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