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

Ronen Alon, Robert C. Fuhlbrigge, Erik B. Finger, Timothy A. Springer

Research output: Contribution to journalArticlepeer-review

174 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)849-865
Number of pages17
JournalJournal of Cell Biology
Volume135
Issue number3
DOIs
StatePublished - Nov 1996

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