L-selectin crosslinking induces integrin-dependent adhesion: evidence for a signaling pathway involving PTK but not PKC.
L-selectin mediates the initial contact of leukocytes with the endothelium prior to extravasation. Here we demonstrate that L-selectin engagement can induce rapid and avid integrin-dependent T cell adhesion to recombinant immobilized cell adhesion molecules (CAMs) including ICAM-1, ICAM-3, and VCAM-1, as well as to the extracellular matrix protein fibronectin (FN). L-selectin-induced adhesion to these integrin ligands shares characteristics with CD3 mAb- or phorbol ester-induced adhesion in requiring metabolic energy, tyrosine kinase and ligand-stimulated Ca2+ channel activity. However, L-selectin-induced adhesion is distinct from that induced by phorbol ester or CD3 crosslinking in being relatively independent of protein kinase C (PKC) activity and actin polymerization. Consistent with the higher levels of L-selectin expression on CD45RA+ (naive) cells, L-selectin crosslinking induces a greater proportion of naive relative to memory cell binding to CAMs and FN. In contrast, exposure to phorbol ester or CD3 crosslinking is more effective in inducing CD45RO+ (memory) cell adhesion. Thus, in addition to its role in leukocyte capture and rolling on the endothelium, L-selectin may contribute to beta 1 and beta 2 integrin-dependent binding and arrest.
Sikorski
M A
MA
Department of Medicine, New England Medical Center, Boston, Massachusetts, USA.
Staunton
D E
DE
Mier
J W
JW
D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003432:Cross-Linking Reagents; D015638:Cytochalasin D; D004734:Energy Metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D006873:Hydroquinones / Q000494:pharmacology; D016023:Integrins / Q000378:metabolism*; D019041:L-Selectin / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000502:physiology*
D015815:Cell Adhesion Molecules; D003432:Cross-Linking Reagents; D004791:Enzyme Inhibitors; D006873:Hydroquinones; D016023:Integrins; D019041:L-Selectin; D015638:Cytochalasin D; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; C048212:erbstatin