Monocyte migration into tissues, an important event in inflammation, requires an intricate interplay between determinants on cell surfaces and extracellular matrix (ECM). Galectin-3 is able to modulate cell-ECM interactions and is an important mediator of inflammation. In this study, we sought to investigate whether interactions established between galectin-3 and ECM glycoproteins are involved in monocyte migration, given that the mechanisms by which monocytes move across the endothelium and through the extravascular tissue are poorly understood. Using the in vitro transwell system, we demonstrated that monocyte migration was potentiated in the presence of galectin-3 plus laminin or fibronectin, but not vitronectin, and was dependent on the carbohydrate recognition domain of the lectin. Only galectin-3-fibronectin combinations potentiated the migration of monocyte-derived macrophages. In binding assays, galectin-3 did not bind to fibronectin, whereas both the full-length and the truncated forms of the lectin, which retains carbohydrate binding ability, were able to bind to laminin. Our results show that monocytes migrate through distinct mechanisms and selective interactions with the extracellular matrix driven by galectin-3. We suggest that the lectin may bridge monocytes to laminin and may also activate these cells, resulting in the positive regulation of other adhesion molecules and cell adhesion to fibronectin. 1. Introduction The migration of peripheral circulating monocytes into tissues is considered an important process in the immune response, including inflammatory reactions. During this process, monocytes migrate from the circulation, across the endothelium and the basement membrane, and into the affected tissue. When monocytes enter tissues, they eventually mature into macrophages to carry out their main functions. As reported concerning other leukocytes, the monocyte migratory response occurs through a multistep adhesion mechanism. Interactions established between leukocytes and extracellular matrix (ECM) components are crucial to the cell migration through the perivascular tissue [1]. Lectins may mediate many of the adhesive interactions during leukocyte extravasation and directly influence the migratory response of these cells [2, 3]. Galectin-3, a -galactoside-binding lectin belonging to the galectin family, is involved in many processes during the inflammatory response [4]. This lectin is expressed and secreted by various inflammatory cells [4] and induces migration of monocytes/macrophages [5]. The mechanisms by which galectin-3 induces
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