Interactions through L-selectin between leukocytes and adherent leukocytes nucleate rolling adhesions on selectins and VCAM-1 in shear flow.
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.
Center for Blood Research, Department of Pathology, Boston, Massachusetts 02115, USA.
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R
Alon
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RC
Fuhlbrigge
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EB
Finger
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TA
Springer
D002448:Cell Adhesion / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D002918:Chymotrypsin; D004730:Endothelium, Vascular / Q000276:immunology; D006801:Humans; D019041:L-Selectin / Q000378:metabolism*; D007962:Leukocytes / Q000166:cytology*; D008024:Ligands; D008562:Membrane Glycoproteins / Q000378:metabolism; D009439:Neuraminidase; D019087:Selectins / Q000378:metabolism*; D014471:Umbilical Veins; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
D008024:Ligands; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D019087:Selectins; D019010:Vascular Cell Adhesion Molecule-1; D019041:L-Selectin; D009439:Neuraminidase; D002918:Chymotrypsin