L-selectin crosslinking induces integrin-dependent adhesion: evidence for a signaling pathway involving PTK but not PKC

Cell Adhes Commun. 1996 Nov;4(4-5):355-67. doi: 10.3109/15419069609010778.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Adhesion / drug effects
  • Cell Adhesion / physiology*
  • Cell Adhesion Molecules / metabolism
  • Cross-Linking Reagents
  • Cytochalasin D
  • Energy Metabolism
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Hydroquinones / pharmacology
  • Integrins / metabolism*
  • L-Selectin / metabolism*
  • Protein Kinase C / antagonists & inhibitors
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Signal Transduction*
  • T-Lymphocyte Subsets / physiology*

Substances

  • Cell Adhesion Molecules
  • Cross-Linking Reagents
  • Enzyme Inhibitors
  • Hydroquinones
  • Integrins
  • L-Selectin
  • Cytochalasin D
  • Protein-Tyrosine Kinases
  • Protein Kinase C
  • erbstatin