RESUMO
El factor de activación plaquetaria es un fosfolípido de síntesis endógena relacionado directamente con diversos procesos como isquemia, necrosis, trombosis y otros. El principal blanco de sus efectos deletéreos se encuentra en las células endoteliales, leucocitos y plaquetas, donde provoca graves perturbaciones mecánicas, reológicas y bioquímicas en la unidad circulatoria. Se realizó una revisión bibliográfica del factor de activación plaquetaria, su síntesis endógena, sus funciones biológicas, con especial énfasis en su relación con el daño oxidativo, así como los principales antagonistas conocidos. Se enfatizó el efecto de los ginkgólidos contenidos en el EGB 761 (extracto de Ginkgo biloba) y su aplicación en la clínica de diversos procesos patológicos relacionados con la circulación cerebral y periférica
Assuntos
Fator de Ativação de Plaquetas/biossíntese , Estresse Oxidativo , Ginkgo biloba , Plantas MedicinaisRESUMO
We investigated the effect of sodium nitroprusside (SNP), a donor of nitric oxide, on the formation of platelet-activating factor (PAF) and uterine contractility in mouse uterine horns from mice treated with estrogen. Because the major pathway of PAF synthesis is the remodeling pathway in uterine tissue, we evaluated the incorporation of 14C-acetate into PAF-like molecules. Our results showed that SNP (100-300 mumol/L) caused a transient increase in the synthesis of PAF, which remained cell-associated. The addition of SNP (100-300 mumol/L) to a mouse uterine horn in an isolated organ bath preparation evoked a transient increase in contractility, which was inhibited by hemoglobin (2 micrograms/mL), a nitric oxide scavenger, but not by methylene blue (10 mumol/L), a guanylate cyclase inhibitor. The pharmacological characteristics of the contractions evoked by SNP resembled those evoked after mast cell activation, in that they were blocked by ritodrine (a beta 2 adrenergic agonist, 0.1 mumol/L); indomethacin (a cyclooxygenase inhibitor, 10 mumol/L); ketotifen (a mast cell stabilizer, 1.0 mumol/L); cromolyn sodium (a mast cell stabilizer, 100 mumol/L); pyrilamine (an H1 antagonist, 10 mumol/L); and ketanserine (5HT2 antagonist, 0.1 mumol/L). These data demonstrate that nitric oxide generated from SNP stimulated the synthesis of PAF and evoked contractility in uterine horns from mice treated with estrogen. This result suggests the possibility that these tissue conditions might be favorable for the generation of peroxynitrites, possible mediators of both effects. It is also shown that the contractility evoked by the addition of SNP was not due to production of PAF, because its antagonist, WEB 2086 (10-30 mumol/L, a concentration that blocked contractions evoked by PAF 1 nmol/L), had no effect on the SNP-evoked contractions.
Assuntos
Estrogênios/farmacologia , Doadores de Óxido Nítrico/farmacologia , Nitroprussiato/farmacologia , Fator de Ativação de Plaquetas/biossíntese , Útero/efeitos dos fármacos , Animais , Radioisótopos de Carbono , Feminino , Liberação de Histamina/efeitos dos fármacos , Técnicas In Vitro , Camundongos , Fator de Ativação de Plaquetas/análogos & derivados , Contração Uterina/efeitos dos fármacos , Útero/metabolismoRESUMO
Infection of rats with the parasite Nippostrongylus brasiliensis results in severe intestinal pathology and dysfunction. Much of the damage that occurs within the intestinal tract may be the direct result of the production of potent inflammatory mediators. PAF is one such lipid mediator that may lead to the altered motility and secretory changes that occur during N. brasiliensis infection. Male, Sprague-Dawley rats were subcutaneously infected with 3000 third stage larvae, while control groups were injected with phosphate buffered saline. At various times post infection (4-42 days) groups of four or more infected and control rats were killed and samples of ileum and jejunum were removed for determination of PAF and leukotriene synthesis (LTB4 and LTC4), myeloperoxidase (MPO) activity and tissue eosinophil and mast cell numbers. Separate groups of rats were killed at similar times for the determination of intestinal worm burden and serum rat mast cell protease II (RMCP-II) levels. Significant elevation in PAF synthesis was not seen until day 15, a time when the intestinal worm burden was no longer evident. Furthermore, this elevation was restricted to the jejunum. The elevation in PAF synthesis correlated with a significant elevation in histologically detectable eosinophils and mast cells in the jejunum. Mast cell activity, as detected through serum concentrations of RMCP-II, was significantly elevated at day 8 post-infection and remained elevated until day 18 post-infection. However, despite significant changes in ileal eosinophil and mast cell numbers, PAF synthesis in the ileum did not differ significantly over the course of the infection. LTB4 and LTC4 production and MPO activity, were significantly elevated in both ileum and jejunum only following worm loss. These results demonstrate that PAF synthesis is altered following primary infection with N. brasiliensis. Changes in PAF synthesis paralleled changes in synthesis of other inflammatory mediators and were associated with hyperplasia of various inflammatory cells. Nevertheless, elevated PAF production is not simply a consequence of intestinal eosinophil and mast cell hyperplasia, as ileal PAF production did not significantly change despite hyperplasia of these cell types.
Assuntos
Íleo/metabolismo , Jejuno/metabolismo , Infecções por Nematoides/metabolismo , Nippostrongylus , Fator de Ativação de Plaquetas/biossíntese , Animais , Degranulação Celular , Quimases , Eosinófilos/citologia , Eosinófilos/metabolismo , Íleo/citologia , Íleo/parasitologia , Jejuno/citologia , Jejuno/parasitologia , Leucotrieno B4/biossíntese , Leucotrienos/biossíntese , Masculino , Mastócitos/metabolismo , Mastócitos/fisiologia , Peroxidase/metabolismo , Ratos , Ratos Endogâmicos , SRS-A/biossíntese , Serina Endopeptidases/sangueRESUMO
Human polymorphonuclear leucocytes (PMN) stimulated with either immune complexes (IC), phorbol myristate acetate (PMA) or N-formyl-methionyl-leucyl-phenylalanine (FMLP) generate platelet-activating factor (PAF-acether). The present study demonstrates that treatment of PMN with recombinant human interferon-gamma (IFN-gamma) significantly enhanced the production of PAF-acether by stimulated cells, in a concentration-dependent mode. On the contrary, alpha and beta IFN were completely unable to increase PAF-acether synthesis by stimulated PMN. The significance of these results is discussed.
Assuntos
Interferon gama/farmacologia , Neutrófilos/metabolismo , Fator de Ativação de Plaquetas/biossíntese , Complexo Antígeno-Anticorpo/fisiologia , Células Cultivadas , Humanos , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Neutrófilos/efeitos dos fármacos , Acetato de Tetradecanoilforbol/farmacologiaRESUMO
1. Seven patients submitted to myocardial revascularization surgery with cardiopulmonary bypass were studied. Blood samples were obtained immediately before and 24 h after surgery. The parameters studied were the production of platelet activating factor (PAF-acether) and superoxide anion, cellular beta-glucuronidase activity as well as polymorphonuclear cell (PMN) and platelet counts. 2. Twenty-four h after surgery, there was a 54% decrease in platelet number (P less than 0.005), a 121% increase in PMN number (P less than 0.005), a 353% increase in PAF-acether (P less than 0.01), a 211% increase in superoxide anion (O2-) and a 104% increase in beta-glucuronidase (P less than 0.05) levels when compared with the pre-surgery levels. 3. The present results indicate that PMN are more reactive after surgery with cardiopulmonary bypass.
Assuntos
Ponte Cardiopulmonar , Glucuronidase/sangue , Revascularização Miocárdica , Neutrófilos/fisiologia , Fator de Ativação de Plaquetas/biossíntese , Superóxidos/sangue , Contagem de Células Sanguíneas , Humanos , Pessoa de Meia-Idade , Contagem de PlaquetasRESUMO
Seven patients submitted to myocardial revascularization surgery with cardiopulmonary bypass were studied. Blood samples were obtained immediately before and 24 h after surgery. The parameters studied were the production of platelet activating factor (PAF-acether) and superoxide anion, cellular beta-glucuronidase activity as well as polymorphonuclear cell(PMN) and platelet count. Twenty-four h after surgery, there was a 54% decrease in platelet number (P<0.005), a 121% increase in PMN number (P<0.005), a 353% increase in PAF-acether (P<0.01), a 211% increase in superoxide anion (O2-) and a 104% increase in beta-glucuronidase (P<0.05) levels when compared with the pre-surgery levels. The present results indicate that PMN are more reactive after surgery with cardiopulmonary bypass