Specific inhibition of T-cell adhesion to extracellular matrix and proinflammatory cytokine secretion by human recombinant galectin-1

The migration of immune cells through the extracellular matrix (ECM) toward s inflammatory sites is co-ordinated by receptors recognizing ECM glycoprot eins, chemokines and proinflammatory cytokines. In this context, galectins are secreted to the extracellular milieu, where they recognize poly-N-acety llactosamine chains on major ECM glycoproteins, such as fibronectin and lam inin. We investigated the possibility that galectin-1 could modulate the ad hesion of human T cells to ECM and ECM components. T cells were purified fr om human blood, activated with interleukin-2 (IL-2), labelled, and incubate d Further with intact immobilized ECM and ECM glycoproteins in the presence of increasing concentrations of human recombinant galectin-1, or its more stable, related, C2-S molecule obtained by site-directed mutagenesis. The p resence of galectin-1 was shown to inhibit T-cell adhesion to intact ECM, l aminin and fibronectin, and to a lesser extent to collagen type IV, in a do se-dependent manner. This effect was specifically blocked by anti-galectin- 1 antibody and was dependent on the lectin's carbohydrate-binding propertie s. The inhibition of T-cell adhesion by galectin-1 correlates with the abil ity of this molecule to block the re-organization of the activated cell's a ctin cytoskeleton. Furthermore, tumour necrosis factor-alpha (TNF-alpha) an d interferon-gamma (IFN-gamma) production was markedly reduced when IL-2-ac tivated T cells were incubated with galectin-1 or its mutant. This effect w as prevented by beta-galactoside-related sugars. The present study reveals an alternative inhibitory mechanism for explaining the suppressive properti es of the galectin-1 subfamily on inflammatory and autoimmune processes.