Negative Regulation of Mast Cell Signaling and Function by the Adaptor LAB/NTAL

Engagement of the Fcɛ receptor I (FcɛRI) on mast cells and basophils initiates signaling pathways leading to degranulation. Early activation events include tyrosine phosphorylation of two transmembrane adaptor proteins, linker for activation of T cells (LAT) and non–T cell activation linker (NTAL; also called LAB; a product of Wbscr5 gene). Previous studies showed that the secretory response was partially inhibited in bone marrow–derived mast cells (BMMCs) from LAT-deficient mice. To clarify the role of NTAL in mast cell degranulation, we compared FcɛRI-mediated signaling events in BMMCs from NTAL-deficient and wild-type mice. Although NTAL is structurally similar to LAT, antigen-mediated degranulation responses were unexpectedly increased in NTAL-deficient mast cells. The earliest event affected was enhanced tyrosine phosphorylation of LAT in antigen-activated cells. This was accompanied by enhanced tyrosine phosphorylation and enzymatic activity of phospholipase C γ1 and phospholipase C γ2, resulting in elevated levels of inositol 1,4,5-trisphosphate and free intracellular Ca2+. NTAL-deficient BMMCs also exhibited an enhanced activity of phosphatidylinositol 3-OH kinase and Src homology 2 domain–containing protein tyrosine phosphatase-2. Although both LAT and NTAL are considered to be localized in membrane rafts, immunogold electron microscopy on isolated membrane sheets demonstrated their independent clustering. The combined data show that NTAL is functionally and topographically different from LAT

Multigenerational study - effect of the selected compounds on the mouse fertility

Several compounds known to be effective for their influence onto the environment were tested. Compounds tested in this study were: benzo/a/ pyrene, lindane (hexachlorocyclohexane isomer), 4-n-nonylphenol, bisphenol A and octachlorostyrene. The question was if these compounds might also function as endocrine disruptors

Hodnocení stavu životního prostředí: Monitoring cizorodých látek v potravních řetězcích:Získání experimentálních dat o vstupu cizorodých látek do životního prostředí

Část 3.c. Hodnocení vlivu cizorodých látek na živé organizmy: Část 1: Vliv cizorodých látek na vývoj preimplatačních stádií embryí savců. Část 2: Studium mutagenity vzorků pylu. Část 3: Hodnocení expozice ryb polyaromatickými uhlovodíky