Enhancement of stromal cell-derived factor-1 alpha-induced chemotaxis for CD4/8 double-positive thymocytes by fibronectin and laminin in mice

Stromal cell-derived factor-1 alpha (SDF-1 alpha) is a chemokine abundantly expressed in the thymus. However, a potential role of SDF-1 alpha in the t hymus has been under consideration, since no appreciable difference was det ected in the migratory responsiveness to the SDF-1 alpha between cortical a nd medullary thymocytes. In the present study, we examined the effects of e xtracellular matrix (ECM) on the responsiveness of murine thymocytes to sev eral chemokines including SDF-1 alpha. In the absence of ECM, chemotactic a ctivity of SDF-1 alpha for cortical (CD4/8 double-positive) thymocytes was almost same as that for medullary (CD4 or CD8 single-positive) thymocytes. In contrast, the chemotactic activity of SDF-1 alpha for cortical thymocyte s was considerably (more than 10-fold) enhanced by laminin or fibronectin a s compared with that for medullary thymocytes. Chemotactic activities of ma crophage-derived chemokine and macrophage inflammatory protein-3 beta for b oth cortical and medullary thymocytes were only slightly enhanced by fibron ectin or laminin. Thus, fibronectin and laminin appear to enhance the chemo tactic activity of SDF-1 alpha for cortical thymocytes selectively. Additio n of a monoclonal antibody against CD29 showed no inhibitory effect on the enhanced chemotactic activity of SDF-1 alpha, suggesting that the other unk nown receptor(s) is involved in this enhancement. Our present data demonstr ate that SDF-1 alpha in the presence of fibronectin or laminin is involved in the distribution of developing thymocytes.