Interactions through L-selectin between leukocytes and adherent leukocytes nucleate rolling adhesions on selectins and VCAM-1 in shear flow.

• DOI: 10.1083/jcb.135.3.849
• Publication Date: 2004-05-15T01:23:47Z
• Authors: R Alon; R C Fuhlbrigge; E B Finger; T A Springer
• Keywords: 0301 basic medicine; Umbilical Veins; Membrane Glycoproteins; Neuraminidase; Vascular Cell Adhesion Molecule-1; Ligands; 03 medical and health sciences; Cell Movement; Cell Adhesion; Leukocytes; Selectins; Chymotrypsin; Humans; Endothelium, Vascular; L-Selectin; Cells, Cultured

We demonstrate an additional step and a positive feedback loop in leukocyte accumulation on inflamed endothelium. Leukocytes in shear flow bind to adherent leukocytes through L-selectin/ligand interactions and subsequently bind downstream and roll on inflamed endothelium, purified E-selectin, P-selectin, L-selectin, VCAM-1, or peripheral node addressin. Thus adherent leukocytes nucleate formation of strings of rolling cells and synergistically enhance leukocyte accumulation. Neutrophils, monocytes, and activated T cell lines, but not peripheral blood T lymphocytes, tether to each other through L-selectin. L-selectin is not involved in direct binding to either E- or P-selectin and is not a major counterreceptor of endothelial selectins. Leukocyte-leukocyte tethers are more tolerant to high shear than direct tethers to endothelial selectins and, like other L-selectin-mediated interactions, require a shear threshold. Synergism between leukocyte-leukocyte and leukocyte-endothelial interactions introduces novel regulatory mechanisms in recruitment of leukocytes in inflammation.