RESUMEN
During an ongoing immune response, immune complexes, composed of Ag, complement factors, and Igs, are formed that can interact with complement receptors (CRs) and IgG Fc receptors (Fc gamma R). The role of CR1/2 and Fc gamma R in the regulation of the immune response was investigated using OVA that was chemically conjugated to whole IgG of the rat anti-mouse CR1/2 mAb 7G6. FACS analysis using the murine B cell lymphoma IIA1.6 confirmed that the 7G6-OVA conjugate recognized CR1/2. Incubating IIA1.6 cells with 7G6-OVA triggered tyrosine phosphorylation and Ag presentation to OVA-specific T cells in vitro. Immunizing mice with 7G6-OVA at a minimal dose of 1 microgram i.p. per mouse markedly enhanced the anti-OVA Ig response, which was primarily of the IgG1 isotype subclass. The 7G6-OVA did not enhance the anti-OVA response in CR1/2-deficient mice. OVA coupled to an isotype control Ab induced a considerably lower anti-OVA response compared with that induced by OVA alone, suggesting inhibition by interaction between the Fc part of the Ab and the inhibitory Fc gamma RIIb on B cells. This findings was supported by the observation that IIA1.6 cells which were incubated with 7G6-OVA lost the ability to present Ag upon transfection with Fc gamma RIIb. In sum, 7G6-conjugated OVA, resembling a natural immune complex, induces an enhanced anti-OVA immune response that involves at least CR1/2-mediated stimulation and that may be partially suppressed by Fc gamma RIIb.
Asunto(s)
Anticuerpos Monoclonales/farmacología , Antígenos/inmunología , Antígenos/metabolismo , Inmunoglobulina G/biosíntesis , Receptores de Complemento 3b/inmunología , Receptores de Complemento 3d/inmunología , Receptores Fc/metabolismo , Animales , Presentación de Antígeno , Antígenos/administración & dosificación , Sitios de Unión de Anticuerpos , Femenino , Inmunoglobulina G/administración & dosificación , Inyecciones Intraperitoneales , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ovalbúmina/administración & dosificación , Ovalbúmina/inmunología , Fosforilación , Receptores de Complemento 3b/metabolismo , Receptores de Complemento 3d/metabolismo , Linfocitos T/inmunología , Linfocitos T/metabolismo , Células Tumorales Cultivadas , Tirosina/metabolismoRESUMEN
The disposition kinetics of amikacin were established in 12 patients with varying degrees of renal impairment (Clcr less than 70 ml/min) after i.m. administration of a dose of 7.5 mg antibiotic/kg body wt. Administered intramuscularly, amikacin follows a single-compartment open kinetic model. A decrease may be observed in the absorption and elimination processes in this kind of patient, and mathematical relationships may be established between the variation in the pharmacokinetic parameters and the creatinine clearance. The decrease observed in the elimination constant of amikacin is similar to that observed after i.v. administration of the antibiotic. A dosage regimen for administration of the antibiotic is proposed for this kind of patient on the basis of desired peak and trough serum levels obtained throughout treatment.