ovalbumin and herbimycin

We examined the effect of two different types of tyrosine kinase inhibitor, herbimycin A and genistein, on antigen-induced tracheal contraction and antigen-induced histamine release from the trachea in sensitized guinea pigs in vitro. Herbimycin A (1-10 microM) and genistein (1-10 microM) significantly inhibited antigen-induced tracheal contraction, compared with control. Additionally, herbimycin A (1-10 microM) and genistein (3-10 microM) significantly inhibited antigen-induced histamine release from the trachea in a concentration-dependent manner, compared with control. On the contrary, herbimycin A and genistein did not suppress acetylcholine- and histamine-induced tracheal contraction. We concluded that herbimycin A and genistein inhibit antigen-induced tracheal contraction without inhibiting smooth muscle contractility, and these inhibitory effects are due to, at least partially, inhibiting histamine release from tracheal mast cells.

Topics: Acetylcholine; Animals; Benzoquinones; Dose-Response Relationship, Drug; Enzyme Inhibitors; Genistein; Guinea Pigs; Histamine; Histamine Release; Isoflavones; Lactams, Macrocyclic; Male; Muscle Contraction; Muscle, Smooth; Ovalbumin; Protein-Tyrosine Kinases; Quinones; Rifabutin; Trachea

Activation of protein-tyrosine kinases (PTKs) is required for signal transduction during T cell activation, although the pathway used during thymic selection is unknown. An in vitro system was established in which T cell receptor transgenic thymocytes underwent clonal deletion in response to peptide antigen. The effects of two PTK-specific inhibitors, herbimycin A and genistein, on the clonal deletion of immature thymocytes and the activation of mature thymocytes were examined. Clonal deletion occurred while T cell activation was inhibited and when no p56lck activity was evident. Thus, p56lck is not required for the antigen-stimulated step of clonal deletion of immature thymocytes, and negative selection proceeds via a distinct pathway.

Topics: Animals; Benzoquinones; Cells, Cultured; Chickens; DNA Replication; Genistein; Isoflavones; L Cells; Lactams, Macrocyclic; Lymphocyte Activation; Lymphocyte Specific Protein Tyrosine Kinase p56(lck); Mice; Mice, Transgenic; Ovalbumin; Protein-Tyrosine Kinases; Quinones; Receptors, Antigen, T-Cell; Rifabutin; Signal Transduction; T-Lymphocyte Subsets; T-Lymphocytes; Transfection