No detectable endothelial- or leukocyte-derived L-selectin ligand activity on the endothelium in inflamed cremaster muscle venules

• L-selectin is important in mediating leukocyte recruitment in inflammation. The role of L-selectin was for long believed to be influenced by an inducible endothelial ligand; however, L-selectin ligand activity was recently shown to be mediated by leukocytic P-selectin glycoprotein ligand 1 (PSGL-1). Still, it is unknown whether PSGL-1 is deposited on the endothelium or whether leukocyte fragments or leukocytic uropods are presented on the venular surface. Moreover, it is unclear whether ligands for L-selectin other than PSGL-1 are present in inflammation. Overall, this has complicated understanding of the mechanisms that guide recruitment of inflammatory cells. Here, I used intravital microscopy on mouse cremaster muscle venules to show that L-selectin influences leukocyte rolling in inflammation exclusively by mediating L-selectin/PSGL-1-dependent, secondary capture to rolling and adherent leukocytes. I show that leukocyte primary capture in inflammation is mediated almost entirely by P-selectin, whereas the capacity of E-selectin to mediate capture appears to be minimal. In parallel, primary capture remaining after function inhibition of P-selectin is not decreased by blockage or absence of L-selectin. Rolling along the endothelium in venules following a number of inflammatory treatments was abolished by simultaneous blockage of P-selectin, E-selectin, and VCAM-1, indicating that there is no additional adhesive pathway involving L-selectin or any other molecule that can mediate leukocyte rolling in inflamed cremaster muscle venules in response to the used stimuli. Moreover, in vivo staining failed to detect any L-selectin ligand activity on the endothelium. These data demonstrate that expression of L-selectin on leukocytes is insufficient for mediating rolling and efficient recruitment of leukocytes in inflammation.

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