Distinct phenotype of E-selectin-deficient mice. E-selectin is required for slow leukocyte rolling in vivo

Circulation Research
E J Kunkel, K Ley

Abstract

Leukocyte capture and rolling are mediated by calcium-dependent lectins expressed on most leukocytes (L-selectin) and the vascular endothelium (P- and E-selectin). To study the role of the selectins during inflammation, we have investigated leukocyte rolling in venules of tumor necrosis factor-alpha (TNF-alpha)-treated mouse cremaster muscles in wild-type mice and gene-targeted mice with homozygous deficiency for L-, P-, or E-selectin (L-/-, P-/-, or E-/-, respectively). TNF-alpha treatment induces expression of E-selectin and increases expression of P-selectin on endothelial cells. Consistent with previous reports of redundant P- and E-selectin function, a combination of monoclonal antibodies (mAbs) against P- and E-selectin (RB40.34 and 9A9, respectively) was necessary to block rolling in wild-type mice. The rolling leukocyte flux fraction (percent rolling cells) in L-/- mice was similar to that in wild-type mice, but rolling in these mice was blocked by a P-selectin mAb. The velocity of rolling leukocytes in TNF-alpha-treated wild-type, P-/-, or L-/- mice was 5 to 10 times slower (3 to 7 microns/s) than during trauma-induced rolling (20 to 50 microns/s). In contrast, leukocytes in venules of TNF-alpha-treated E-/- mice rolle...Continue Reading

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Jun 5, 2008·Inflammatory Bowel Diseases·Jesús Rivera-NievesKlaus Ley
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