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Biomedical subjects

G Cremaschi

Publications and source records attributed to G Cremaschi.

26 records · Page 2Linked to original sources
PubMed1988

Molecular and biological interaction between major histocompatibility complex class I antigens and luteinizing hormone receptors or beta-adrenergic receptors triggers cellular response in mice.

Purified IgG from BALB/c mouse anti-C3H serum exerts positive inotropic and chronotropic effects in C3H mouse atria and induces testosterone synthesis in C3H mouse Leydig cells. The effect depends on IgG concentration and can be abolished by beta-adrenergic-receptor and luteinizing hormone-receptor antagonists. IgG interferes with the binding of dihydroalprenolol and luteinizing hormone. Monoclonal antibodies against major histocompatibility complex class I antigens were active on the Leydig cells of C3H and BALB/c mice. There was a parallelism between the effect of each individual monoclonal antibody with specificity for a particular haplotype and the response of the target cell from the strains carrying such haplotypes. These antibodies could precipitate the soluble luteinizing hormone-receptor complex. The results suggested that bound hormone triggers the association of major histocompatibility class I antigen with the receptor, thereby activating the respective target cells.

Animals↗
PubMed1988

Antibodies to beta 1 and beta 2 adrenoreceptors in Chagas' disease.

Evidence accumulated over the last decade concerning human and experimental models suggests that an immunopathological mechanism may be involved in the pathogenesis of chronic Chagas' disease. In this paper we demonstrate the existence of two different circulating IgG in chagasic patients which bind with myocardial beta 1 and spleen cell beta 2 adrenoceptors, acting as non-competitive inhibitors. Both chagasic IgG against beta 1 and beta 2 adrenoceptor increased intracellular levels of cAMP that could be blocked by specific beta 1 and beta 2 adrenoceptor antagonists. The specificity for beta 1 and beta 2 adrenoceptors and the independence of other tissue reactive antibodies was demonstrated by IgG absorption with turkey red blood cell (TRBC), human lymphocytes (HL) or guinea pig red blood cells (GPRBC). The F(ab')2 fraction acted similarly. This supports the specificity of beta 1 and beta 2 adrenoceptors to the chagasic IgG and the independence of the other tissue reactive antibodies, such as EVI system. The probable pathogenic role of both beta 1 and beta 2 adrenergic chagasic antibody is discussed.

Antibody Specificity↗
PubMed1985

Alloimmunization-induced changes in thymocytes' prostaglandin levels: a signal for the induction of biological activity.

The effect of BALB/c anti C3H non-adherent thymocytes on the spontaneous activity of isolated C3H mouse atria was studied. Immune non-adherent thymocytes alone induced negative inotropic action, while macrophages alone did not have any effect. The same kind of collaborative effect between both cells is described. Cell-free supernatants obtained from non-adherent immune cells incubated with C3H myocardium induced the same biological activity than immune non-adherent thymocytes indicating that a soluble factor is involved. Inhibition of non-adherent thymocytes' cyclo-oxygenase activity prevented the negative inotropic effect of immune cells or cell-free supernatants. In contrast, when the inhibitors were applied upon myocardium did not modify the response. Supernatants from immune thymocytes plus myocardium, release higher amount of PGE series than those from non-immune thymocytes. It is proposed that non-adherent thymocytes are able to synthesize and release PGE series upon recognition of alloantigens expressed by atria cells; which in turn triggers the negative inotropic effect.

Animals↗
PubMed1985

Prostaglandins, cyclic AMP production and biological activity of alloimmune thymocytes.

The effect of alloimmunized non-adherent thymocytes on the spontaneous activity of the mouse atria was studied. BALB/c anti C3H non-adherent thymocytes induced negative inotropic effect on C3H atria. Cell-free supernatant from non-adherent thymocytes induced the same biological activity. This activity was blunted by the inhibition of non-adherent immune thymocytes' cyclo-oxygenase activity. PGE was present in higher amounts in free-cell supernatant from BALB/c anti C3H thymocytes plus C3H atria than in those from non-immune thymocytes. Intracellular levels of immune thymocytes cAMP are raised in comparison with those of normal thymocytes. It is proposed that alloantigen stimulates non-adherent thymocytes, increasing intracellular levels of cAMP and PGE. Immune thymocytes, release PGE upon recognition of the alloantigens expressed in the atria and this triggers a negative inotropic effect. The increment in immune thymocyte cAMP appears to be associated with the activation of thymocytes cyclo-oxygenase activity by alloimmunization.

Animals↗
PubMed1984

Variable inotropic effect of immune cells on mice atria--participation of metabolic products of arachidonic acid.

The effect of BALB/c anti CF1 lymph node cells and thymocytes on the spontaneous activity of isolated CF1 mouse atria was studied. Immune lymph node cells induced opposite effects depending on the number of immunizations. Immune lymph node cells from mice which received two immunizations decreased the contractile tension of the atrium, whereas, cells from mice exposed to three and five immunizations strongly increased the tension. Immune thymocytes induced only negative inotropic action and this effect did not depend on the number of immunizations. Indeed, it was similar after two, three or five immunizations. Control normal lymph node cells or thymocytes from BALB/c or CF1 mice had no effect on CF1 atria. Furthermore, BALB/c anti CF1 cells had no effect on BALB/c atria. Inhibitors of cyclooxygenase activity prevented the negative inotropic influence of immune thymocytes and lymph node cells seen after two immunizations. In contrast, inhibitors of the lipoxygenase pathway abolished the positive inotropic action induced by lymph node cells obtained after three and five immunizations. Cell-free supernatants of lymph node cells from animals receiving five immunizations, stimulated the contractile activity of atrium, while those from thymocytes inhibited it, indicating that soluble factors are generated by contact of immune cells with the myocardium. It is proposed that upon recognition of alloantigens expressed by atrial cells, lymph node cells and thymocytes are activated and release either arachidonic acid metabolites or some factor(s) that induces this release by other cells, which in turn triggers different effects in myocardial tissue depending on the set of cells involved in the primary immune response.

Animals↗
PubMed1984

Alloimmune IgG binds and modulates cardiac beta-adrenoceptor activity.

Purified IgG from murine alloimmune sera directed against class I products from the major histocompatibility complex of the mouse, could bind to the beta-adrenoceptors and stimulate contractile activity of myocardium. Immune IgG inhibited the binding of (-) 3H-DHA to beta-adrenoceptors of mouse myocardial membranes behaving as a competitive inhibitor. Moreover, immune IgG induced positive inotropic and chronotropic effects on isolated mouse atria. These effects could be blocked by beta-adrenoceptors antagonists. Data prove that immune IgG directed against specific alloantigens are able to recognize the beta-adrenoceptors and mimic the stimulation of the beta-adrenoceptor agonist.

Animals↗
PubMedDate not supplied

Involvement of nitric oxide synthase and protein kinase C activation on chagasic antibodies action upon cardiac contractility.

We have already demonstrated the presence of antibodies in the sera of chagasic patients with the ability to interact with neurotransmitter receptors triggering several intracellular pathways of transduction signals. Here we show that, chagasic IgG induced protein kinase C (PKC) translocation to rat cardiac membranes and this effect was inhibited by muscarinic cholinergic blockers atropine and AF-DX 116 pointing to the participation of M2 receptors in this effect. It was also able to stimulate nitric oxide synthase (NOS) activity and this action was blunted by phospholipase C (PLC) and PKC inhibitors indicating that the production of nitric oxide (NO) would be the consequence of the cascade of enzymatic pathways triggered by mAChR activation. PKC and NOS activities were involved in chagasic IgG negative inotropic actions on rat isolated myocardium as its effects were blunted by staurosporine and L-N-monomethyl arginine. Furthermore, low concentrations of chagasic IgG inhibited the cardiac mechanical action of carbachol in a non-competitive manner. These data suggested that PKC activation in myocardium by chagasic IgG would be involved in its physiological actions by modulating NOS activity. The participation of PKC-mediated phosphorylation of mAChR leading to receptor desensitization as one of the causes of dysautonomia is also discussed.

Animals↗