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

Summary Stromal cell-derived factor-1α (SDF-1α) is a chemokine abundantly expressed in the thymus. However, a potential role of SDF-1α in the thymus has been under consideration, since no appreciable difference was detected in the migratory responsiveness to the SDF-1α between cortical and medullary thymocytes. In the present study, we examined the effects of extracellular matrix (ECM) on the responsiveness of murine thymocytes to several chemokines including SDF-1α. In the absence of ECM, chemotactic activity of SDF-1α 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-1α for cortical thymocytes was considerably (more than 10-fold) enhanced by laminin or fibronectin as compared with that for medullary thymocytes. Chemotactic activities of macrophage-derived chemokine and macrophage inflammatory protein-3β for both cortical and medullary thymocytes were only slightly enhanced by fibronectin or laminin. Thus, fibronectin and laminin appear to enhance the chemotactic activity of SDF-1α for cortical thymocytes selectively. Addition of a monoclonal antibody against CD29 showed no inhibitory effect on the enhanced chemotactic activity of SDF-1α, suggesting that the other unknown receptor(s) is involved in this enhancement. Our present data demonstrate that SDF-1α in the presence of fibronectin or laminin is involved in the distribution of developing thymocytes.