Assuntos
Infecção Hospitalar/epidemiologia , Antibioticoprofilaxia , Argentina/epidemiologia , Infecção Hospitalar/prevenção & controle , Hospitais de Ensino , Humanos , Controle de Infecções/organização & administração , Modelos Lineares , Prevalência , Fatores de Risco , Procedimentos Cirúrgicos OperatóriosRESUMO
We investigated the in vitro action of the bile pigments, unconjugated bilirubin (UB) and bilirubin monoglucuronide (BMG) on complement (C) cascade reaction. Both UB and BMG inhibited hemolysis in the classical pathway (CP) in a dose-dependent manner at low micromolar concentrations, UB showing a stronger effect than BMG. The analysis of the action of UB on the hemolytic activity of the C1, C4, C2 and C-EDTA components of the C cascade revealed that the C1 step was the most inhibited. An enzyme immunoassay was developed to evaluate the effect of UB on the binding of C1q, one of the subcomponents of C1, to human IgM and IgG. The study demonstrated that the unconjugated pigment interferes both the C1q-IgM and -IgG interactions, thus tentatively explaining the inhibitory action of UB on hemolytic activity of C1. We conclude that the anti-complement effect of UB is mainly exerted on the C1 component, the recognition unit of CP. The potential clinical implication of the reported effects in hyperbilirubinemia is discussed.
Assuntos
Bilirrubina/farmacologia , Proteínas Inativadoras do Complemento/farmacologia , Proteínas do Sistema Complemento/imunologia , Hemólise/efeitos dos fármacos , Animais , Bilirrubina/análogos & derivados , Células Cultivadas , Complemento C1/imunologia , Complemento C1q/imunologia , Eritrócitos/efeitos dos fármacos , Humanos , Técnicas Imunoenzimáticas , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , OvinosRESUMO
The effect of complement (C) on the erythrocyte deformability was investigated. Sheep erythrocytes (E) were sensitized with specific antibodies (A) and treated with various doses of human C. Gravity filtration of unlysed EAC showed a C dose-dependent decrease in whole cell deformability, which was shown to be due to an impairment of the membrane rheological properties. As the fluidity of the lipid bilayer, sensed by a spin label, was not modified, the observed effects should be related to an interaction between C and the cytoskeleton. The influence of C3b and C3d in these processes seems unlikely, as similar hemagglutination titers were found, respectively, for anti-C3c and anti-C3d antisera against the varying EAC. The study of the degree of spontaneous hemolysis of EAC in buffers with solutes of different Stokes radii showed that differing-sized functional C lesions were produced, and that the formation of larger-sized lesions was favored by incubation with higher C doses. These results suggest that the insertion of proteins from the membrane attack complex, C5b-9 (MAC), into the erythrocyte membrane may be responsible for the effect of C on the rheological properties of the erythrocyte membrane.
