ENHANCEMENT OF VLA INTEGRIN RECEPTOR FUNCTION ON THYMOCYTES BY CAMP IS DEPENDENT ON THE MATURATION STAGE OF THE THYMOCYTES

A class of adhesion molecules, the VLA integrins, are expressed on thy mocytes and have been shown to affect immature thymocyte differentiati on in vitro. This study examines the ability of cAMP to regulate VLA r eceptor function in thymocytes. Pharmacologic agents that raise intrac ellular cAMP enhanced the binding of immature CD4(-) CD8(-) and CD4(+) . CD8(+) thymocytes to fibronectin while having no effect on the bindi ng of the more mature Jlld(-) thymocytes. PGE(2), a hormone produced b y thymic epithelial cells and known to raise intracellular cAMP levels in thymocytes, also increased the binding of immature thymocytes to f ibronectin. In contrast, activation of protein kinase C via PMA enhanc ed the binding of all three thymocyte subsets. The cAMP-induced bindin g was blocked by mAbs to the VLA integrin chains alpha(4) and alpha(5) and by the protein kinase A (PKA) inhibitor, (Rp)-cAMPS, indicating t hat activation of PKA enhances VLA-4 and VLA-5 receptor function. Acti vation of PKA was induced in all three thymocyte subsets following add ition of cAMPa or forskolin, indicating that the inability of cAMP to enhance the binding of Jlld(-) thymocytes was not due to an inability to activate PKA. Thus, cAMP enhances integrin function in thymocytes i n a maturation stage-specific manner.