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 thymocytes and have been shown to affect immature thymocyte differentiation in vitro. This study examines the ability of cAMP to regulate VLA receptor function in thymocytes. Pharmacologic agents that raise intracellular cAMP enhanced the binding of immature CD4- CD8- and CD4+ CD8+ thymocytes to fibronectin while having no effect on the binding of the more mature JIId- thymocytes. PGE2, a hormone produced by thymic epithelial cells and known to raise intracellular cAMP levels in thymocytes, also increased the binding of immature thymocytes to fibronectin. In contrast, activation of protein kinase C via PMA enhanced the binding of all three thymocyte subsets. The cAMP-induced binding 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 that activation of PKA enhances VLA-4 and VLA-5 receptor function. Activation of PKA was induced in all three thymocyte subsets following addition of cAMPa or forskolin, indicating that the inability of cAMP to enhance the binding of JIId- thymocytes was not due to an inability to activate PKA. Thus, cAMP enhances integrin function in thymocytes in a maturation stage-specific manner.
Halvorson
M J
MJ
Laboratory of Molecular Structure, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
Coligan
J E
JE
D000818:Animals; D015704:CD4 Antigens / Q000096:biosynthesis; D018956:CD5 Antigens / Q000096:biosynthesis; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology*; D005260:Female; D005353:Fibronectins / Q000502:physiology; D039041:Integrin alpha4beta1; D016023:Integrins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D017469:Receptors, Fibronectin / Q000502:physiology*; D016201:Receptors, Lymphocyte Homing / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology*
D015704:CD4 Antigens; D018956:CD5 Antigens; D005353:Fibronectins; D039041:Integrin alpha4beta1; D016023:Integrins; D017469:Receptors, Fibronectin; D016201:Receptors, Lymphocyte Homing; D000242:Cyclic AMP