Salicylates Inhibit Adhesion and Transmigration of T Lymphocytes by Preventing Integrin Activation Induced by Contact With Endothelial Cells

• Published in: Blood Vol. 92; no. 7; pp. 2389 - 2398
• Main Authors: Gerli, Roberto, Paolucci, Cristina, Gresele, Paolo, Bistoni, Onelia, Fiorucci, Stefano, Muscat, Christopher, Belia, Silvia, Bertotto, Alberto, Costantini, Vincenzo
• Format: Journal Article
• Language: English
• Published: 01.10.1998
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V92.7.2389.2389_2389_2398

The inhibition of cyclooxygenase does not fully account for the spectrum of activities of nonsteroidal antiinflammatory drugs. It is evident, indeed, that regulation of inflammatory cell function may contribute in explaining some of the effects of these drugs. Tissue recruitment of T cells plays a key role in the development of chronic inflammation. Therefore, the effects of salicylates on T-cell adhesion to and migration through endothelial cell monolayers on collagen were analyzed in an in vitro static system. Aspirin and sodium salicylate reduced the ability of unstimulated T cells to adhere to and transmigrate through cytokine-activated endothelium. Although salicylates did not modify the expression of integrins on T cells, they blunted the increased adherence induced by the anti-β2monoclonal antibody (MoAb) KIM127 and prevented the appearance of an activation-dependent epitope of the CD11/CD18 complex, recognized by the MoAb 24, induced by contact with endothelial cells. Salicylates also induced an increase of intracellular calcium ([Ca2+]i) and activation of protein kinase C (PKC) in T cells, but not cell proliferation and interleukin (IL)-2 synthesis. The reduction of T-cell adhesiveness appears to be dependent on the increase in[Ca2+]i levels, as it could be reversed by blocking Ca2+ influx, but not by inhibiting PKC. Moreover, ionomycin at concentrations giving an increase in [Ca2+]i similar to that triggered by aspirin, strictly reproduced the T-cell phenotypic and functional changes induced by salicylates. Aspirin reduced T-cell adhesion and migration also ex vivo after infusion to healthy volunteers. These data suggest that the antiinflammatory activity of salicylates may be due, at least in part, to an interference with the integrin-mediated binding of resting T lymphocytes to activated endothelium with consequent reduction of a specific T-cell recruitment into inflammatory sites.