L-Selectin Crosslinking Induces Integrin-Dependent Adhesion: Evidence for a Signaling Pathway Involving PTK but not PKC

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 Ca⁺⁺ 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 β1 and β2 integrin-dependent binding and arrest.

Key Words:

• Selectin
• Integrin
• Cell Adhesion
• Signaling
• Lymphocyte
• Metabolic Inhibitors