Lysophosphatidic acid receptor-selective effects on Jurkat T cell migration through a Matrigel model basement membrane.
Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) from platelets and mononuclear phagocytes mediate T cell functions through endothelial differentiation gene-encoded G protein-coupled receptors (Edg Rs) specific for LPA (Edg-2, -4, and -7) or S1P (Edg-1, -3, -5, -6, and -8). Jurkat leukemic T cells with the SV40 virus large T Ag (Jurkat-T cells) express Edg-3>-2>-4 Rs, as assessed by RT-semiquantitative PCR and Western blots with anti-Edg R mAbs. Jurkat-T cells expressing predominantly Edg-2 R (Jurkat-T-2 cells) and Edg-4 R (Jurkat-T-4 cells) were developed by cotransfection with the respective sense plasmids and a mixture of antisense plasmids for the other Edg Rs, and hygromycin selection. Migration of Jurkat-T-4 cells, but not Jurkat-T-2 cells, through a layer of Matrigel on a 5-um pore polycarbonate filter was stimulated up to 5-fold by 10(-9) to 10(-6) M LPA and by 30-300 ng/ml of anti-Edg-4 R Ab, but not anti-Edg-2 R Ab. LPA and anti-Edg-4 R Ab also enhanced by up to 4-fold the expression of matrix metalloproteinase by Jurkat-T-4 cells, but not Jurkat-T-2 cells, as assessed by cleavage of [(3)H]-type IV human collagen in the Matrigel. Enhancement of matrix metalloproteinase-dependent trans-Matrigel migration of Jurkat-T cells by the chemokine RANTES was suppressed by anti-Edg-2 R Abs, but was stimulated by anti-Edg-4 R Abs. The opposite effects of Edg-2 and Edg-4 LPA receptors on trans-Matrigel migration and some other T cell functions provide receptor-selective mechanisms for regulation of T cell recruitment and immune contributions.
Zheng
Y
Y
Department of Medicine, University of California Medical Center, San Francisco, CA 94143, USA.
Kong
Y
Y
Goetzl
E J
EJ
D000911:Antibodies, Monoclonal / Q000502:physiology; D001485:Basement Membrane / Q000201:enzymology / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology*; D003094:Collagen; D004338:Drug Combinations; D005109:Extracellular Matrix / Q000201:enzymology / Q000276:immunology; D006801:Humans; D019169:Jurkat Cells; D007797:Laminin; D008246:Lysophospholipids / Q000378:metabolism / Q000502:physiology*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D018448:Models, Immunological; D009687:Nuclear Proteins / Q000235:genetics; D011509:Proteoglycans; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics; D014162:Transfection
D000911:Antibodies, Monoclonal; D004338:Drug Combinations; D007797:Laminin; D008246:Lysophospholipids; D009687:Nuclear Proteins; D011509:Proteoglycans; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D014157:Transcription Factors; C059485:matrigel; D003094:Collagen; D020782:Matrix Metalloproteinases