T cell aggregation induced through CD43: intracellular signals and inhibition by the immunomodulatory drug leflunomide.
The CD43 coreceptor molecule has been shown to participate in lymphocyte adhesion and activation. Leukocyte homotypic aggregation results from a cascade of intracellular signals delivered to the cells upon engagement of different cell-surface molecules with their natural ligands. This phenomenon requires an active metabolism, reorganization of the cytoskeleton, and relocalization of cell-surface molecules. The aim of this study was to identify some of the key members of the signaling cascade leading to T lymphocyte homotypic aggregation following CD43 engagement. CD43-mediated homotypic aggregation of T lymphocytes required the participation of Src kinases, phospholipase C-gamma2, protein kinase C, phosphatidylinositol-3 kinase, as well as extracellular-regulated kinase 1/2 and p38. Data shown here suggest that these signaling molecules play a central role in regulating actin cytoskeleton remodeling after CD43 ligation. We also evaluated the ability of immunomodulatory drugs such as leflunomide to block the CD43-mediated homotypic aggregation. Leflunomide blocked the recruitment of targets of the Src family kinases as well as actin polymerization, diminishing the ability of T lymphocytes to aggregate in response to CD43-specific signals, suggesting that this drug might control the migration and recruitment of lymphoid cells to inflamed tissues.
Layseca-Espinosa
Esther
E
Instituto de Biotecnología, UNAM, Cuernavaca, Morelos 62250, Mexico.
Pedraza-Alva
Gustavo
G
Montiel
José Luis
JL
del Río
Roxana
R
Fierro
Nora A
NA
González-Amaro
Roberto
R
Rosenstein
Yvonne
Y
D000199:Actins / Q000378:metabolism; D015703:Antigens, CD; D002449:Cell Aggregation; D004792:Enzyme Precursors / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins; D007555:Isoxazoles / Q000494:pharmacology*; D019169:Jurkat Cells; D000077339:Leflunomide; D051917:Leukosialin; D008213:Lymphocyte Activation; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051966:Phospholipase C gamma; D011493:Protein Kinase C / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012795:Sialoglycoproteins / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D000072377:Syk Kinase; D013601:T-Lymphocytes / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases; D019061:src-Family Kinases / Q000378:metabolism
D000199:Actins; D015703:Antigens, CD; D004792:Enzyme Precursors; D007166:Immunosuppressive Agents; D047908:Intracellular Signaling Peptides and Proteins; D007555:Isoxazoles; D000077339:Leflunomide; D051917:Leukosialin; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; D051966:Phospholipase C gamma; D011493:Protein Kinase C; D011505:Protein-Tyrosine Kinases; D012795:Sialoglycoproteins; D000072377:Syk Kinase; D010738:Type C Phospholipases; D048051:p38 Mitogen-Activated Protein Kinases; D019061:src-Family Kinases; C465014:SPN protein, human; C000606896:SYK protein, human