The Isoelectric Focusing of Creatine Kinase Variants: II. The Heterogeneity of Creatine Kinase in Human Serum with Normal and Elevated Catalytic Concentrations

Peer Reviewe

The Isoelectric Focusing of Creatine Kinase Variants: I. The Heterogeneity of Creatine Kinase in Human Heart Cytosol and Mitochondria

Peer Reviewe

Exosomes Derived from M. Bovis BCG Infected Macrophages Activate Antigen-Specific CD4+ and CD8+ T Cells In Vitro and In Vivo

Activation of both CD4+ and CD8+ T cells is required for an effective immune response to an M. tuberculosis infection. However, infected macrophages are poor antigen presenting cells and may be spatially separated from recruited T cells, thus limiting antigen presentation within a granuloma. Our previous studies showed that infected macrophages release from cells small membrane-bound vesicles called exosomes which contain mycobacterial lipid components and showed that these exosomes could stimulate a pro-inflammatory response in naïve macrophages. In the present study we demonstrate that exosomes stimulate both CD4+ and CD8+ splenic T cells isolated from mycobacteria-sensitized mice. Although the exosomes contain MHC I and II as well as costimulatory molecules, maximum stimulation of T cells required prior incubation of exosomes with antigen presenting cells. Exosomes isolated from M. bovis and M. tuberculosis infected macrophages also stimulated activation and maturation of mouse bone marrow-derived dendritic cells. Interestingly, intranasal administration of mice with exosomes isolated from M. bovis BCG infected macrophages induce the generation of memory CD4+ and CD8+ T cells. The isolated T cells also produced IFN-γ upon restimulation with BCG antigens. The release of exosomes from infected macrophages may overcome some of the defects in antigen presentation associated with mycobacterial infections and we suggest that exosomes may be a promising M. tuberculosis vaccine candidate

Inhibition of creatine kinase by creatinine phosphate

AbstractCreatinine phosphate was shown to be no substrate of purified creatine kinase from skeletal muscle or of creatine kinase in heart muscle homogenate. It was found to be a competitive inhibitor with respect to creatine phosphate and a noncompetitive inhibitor with respect to ADP