NEUROPEPTIDES, VIA SPECIFIC RECEPTORS, REGULATE T-CELL ADHESION TO FIBRONECTIN

The ability of T cells to adhere to and interact with components of th e blood vessel walls and the extracellular matrix is essential for the ir extravasation and migration into inflamed sites. We have found that the beta(1) integrin-mediated adhesion of resting human T cells to fi bronectin, a major glycoprotein component of the extracellular matrix, is induced by physiologic concentrations of three neuropeptides: calc itonin gene-related protein (CGRP), neuropeptide Y, and somatostatin; each acts via its own specific receptor on the T cell membrane. In con trast, substance P (SP), which coexists with CGRP in the majority of p eripheral endings of sensory nerves, including those innervating the l ymphoid organs, blocks T cell adhesion to fibronectin when induced by CGRP, neuropeptide Y, somatostatin, macrophage inflammatory protein-1 beta, and PMA. Inhibition of T cell adhesion was obtained both by the intact SP peptide and by its 1-4 N-terminal and its 4-11, 5-11, and 6- 11 C-terminal fragments, used at similar nanomolar concentrations. The inhibitory effects of the parent SP peptide and its fragments were ab rogated by an SP NK-1. receptor antagonist, suggesting they all act th rough the same SP NK-1 receptor. These findings suggest that neuropept ides, by activating their specific T cell-expressed receptors, can pro vide the T cells with both positive (proadhesive) and negative (antiad hesive) signals and thereby regulate their function. Thus, neuropeptid es may influence diverse physiologic; processes involving integrins, i ncluding leukocyte-mediated migration and inflammation.