Altered expression and functional profile of lysophosphatidic acid receptors in mitogen-activated human blood T lymphocytes.
Lysophosphatidic acid (LPA) from platelets and mononuclear phagocytes regulates T cell functions through endothelial differentiation gene-encoded G protein-coupled receptors (Edg Rs). Human blood unactivated CD4+ T cells express predominant ly Edg-4 LPA R over marginal levels of Edg-2 LPA R, as assessed by semiquantitative PCR and Western blots. After mitogen activation, the CD4+ T cells express Ed g-2 Rs at approximately one half the level of Edg-4 Rs. Secretion of IL-2 by unactivated Edg-4 R-predominant CD4+ T cells incubated with anti-CD3 plus anti-CD28 antibodies was suppressed significantly and by up to 60% by 10-10 M to 10-6 M LPA, whereas secretion of IL-2 by mitogen-activated Edg-2 R and Edg-4 R codominant CD4+ T cells was enhanced by up to twofold by the same concentrations of LPA. The possibility that the two Edg Rs transduce different LPA signals to CD4+ T cells was supported by findings that IL-2 secretion was inhibited by mouse anti-Edg-4 R monoclonal antibody, but enhanced by mouse anti-Edg-2 R monoclonal antibody. The separate effects of each LPA R were studied in Jurkat T cell transfectants expressing principally human Edg-2 Rs (Jurkat-T-2) or Edg-4 Rs (Jurkat-T-4) and stimulated with anti-CD3 plus phorbol myristate acetate. LPA and anti-Edg-4 R antibody suppressed IL-2 secretion by stimulated Jurkat-T-4 cells, whereas LPA and anti-Edg-2 R antibody enhanced IL-2 secretion by stimulated Jurkat-T-2 cells. Activation-induced alterations in the relative levels of Edg-2 and -4 Rs on CD4+ T cells thus reverse the effects of LPA on T cell receptor-stimulated generation of IL-2.
Zheng
Y
Y
Department of Medicine, University of California Medical Center, San Francisco, California 94143-0711, USA.
Voice
J K
JK
Kong
Y
Y
Goetzl
E J
EJ
D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000276:immunology*; D008246:Lysophospholipids / Q000494:pharmacology*; D008934:Mitogens; D018448:Models, Immunological; D011956:Receptors, Cell Surface / Q000096:biosynthesis*; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D015854:Up-Regulation
D007376:Interleukin-2; D008246:Lysophospholipids; D008934:Mitogens; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid