TY - JOUR
T1 - The roles of L-selectin, β7 integrins, and P-selectin in leukocyte rolling and adhesion in high endothelial venules of Peyer's patches
AU - Kunkel, Eric J.
AU - Ramos, Carroll L.
AU - Steeber, Douglas A.
AU - Müller, Werner
AU - Wagner, Norbert
AU - Tedder, Thomas F.
AU - Ley, Klaus
PY - 1998/9/1
Y1 - 1998/9/1
N2 - Lymphocyte trafficking into Peyer's patches requires β7 integrins and L-selectin. Here, we use intravital microscopy to examine leukocyte rolling and adhesion in Peyer's patch high endothelial venules (HEV) of wild-type, L- selectin-deficient (L(-/-)), β7 integrin-deficient (β7(-/-)), and β7/L(-/-) mice. Although the leukocyte rolling flux fraction was reduced by 70%, Peyer's patches in L(-/-) mice were of normal size and cellularity. In β7(-/-) 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 β7(-/-) mice, suggesting that β7 integrins and L-selectin mediate rolling in Peyer's patch HEV at different velocities. β7/L(-/-) exhibited both a low rolling flux fraction and low adhesion and had severely reduced Peyer's 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 Peyer's patches of wild-type mice expressed functional ligands for P- selectin, and this fraction was increased to 57% in β7/L(-/-) mice. Peyer's 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 Peyer's patches. In situ, β7 integrins and L-selectin account for all lymphocyte homing to Peyer's patches, but P- selectin-dependent rolling, as induced by minimal trauma, may support trafficking of effector T lymphocytes to Peyer's patches.
AB - Lymphocyte trafficking into Peyer's patches requires β7 integrins and L-selectin. Here, we use intravital microscopy to examine leukocyte rolling and adhesion in Peyer's patch high endothelial venules (HEV) of wild-type, L- selectin-deficient (L(-/-)), β7 integrin-deficient (β7(-/-)), and β7/L(-/-) mice. Although the leukocyte rolling flux fraction was reduced by 70%, Peyer's patches in L(-/-) mice were of normal size and cellularity. In β7(-/-) 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 β7(-/-) mice, suggesting that β7 integrins and L-selectin mediate rolling in Peyer's patch HEV at different velocities. β7/L(-/-) exhibited both a low rolling flux fraction and low adhesion and had severely reduced Peyer's 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 Peyer's patches of wild-type mice expressed functional ligands for P- selectin, and this fraction was increased to 57% in β7/L(-/-) mice. Peyer's 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 Peyer's patches. In situ, β7 integrins and L-selectin account for all lymphocyte homing to Peyer's patches, but P- selectin-dependent rolling, as induced by minimal trauma, may support trafficking of effector T lymphocytes to Peyer's patches.
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M3 - Article
C2 - 9725243
AN - SCOPUS:0032169209
SN - 0022-1767
VL - 161
SP - 2449
EP - 2456
JO - Journal of Immunology
JF - Journal of Immunology
IS - 5
ER -