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) towards inflammatory sites is co-ordinated by receptors recognizing ECM glycoproteins, chemokines and proinflammatory cytokines. In this context, galectins are secreted to the extracellular milieu, where they recognize poly-N-acetyllactosamine chains on major ECM glycoproteins, such as fibronectin and laminin. We investigated the possibility that galectin-1 could modulate the adhesion of human T cells to ECM and ECM components. T cells were purified from human blood, activated with interleukin-2 (IL-2), labelled, and incubated 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 presence of galectin-1 was shown to inhibit T-cell adhesion to intact ECM, laminin and fibronectin, and to a lesser extent to collagen type IV, in a dose-dependent manner. This effect was specifically blocked by anti-galectin-1 antibody and was dependent on the lectin's carbohydrate-binding properties. The inhibition of T-cell adhesion by galectin-1 correlates with the ability of this molecule to block the re-organization of the activated cell's actin cytoskeleton. Furthermore, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) production was markedly reduced when IL-2-activated T cells were incubated with galectin-1 or its mutant. This effect was prevented by beta-galactoside-related sugars. The present study reveals an alternative inhibitory mechanism for explaining the suppressive properties of the galectin-1 subfamily on inflammatory and autoimmune processes.
Rabinovich
G A
GA
*Department of Clinical Biochemistry, Faculty of Chemical Sciences, National University of Cordoba, Argentina.
Ariel
A
A
Hershkoviz
R
R
Hirabayashi
J
J
Kasai
K I
KI
Lider
O
O
D002448:Cell Adhesion / Q000187:drug effects; D018929:Cell Culture Techniques; D016207:Cytokines / Q000378:metabolism*; D004306:Dose-Response Relationship, Immunologic; D005109:Extracellular Matrix / Q000276:immunology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D037483:Galectin 1; D006388:Hemagglutinins / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; D016326:Extracellular Matrix Proteins; D037483:Galectin 1; D006388:Hemagglutinins; D011994:Recombinant Proteins