The Reduced Bactericidal Function of Complement C5-Deficient Murine Macrophages Is Associated with Defects in the Synthesis and Delivery of Reactive Oxygen Radicals to Mycobacterial Phagosomes

摘要: Complement C5-deficient (C5(-/-)) macrophages derived from B.10 congenic mice were found to be defective in killing intracellular Mycobacterium tuberculosis (MTB). They bacteriostatic after activation with IFN-gamma alone but bactericidal the combined presence of and C5-derived C5a anaphylatoxin that was deficient among these macrophages. Reduced correlated a decreased production reactive oxygen species (ROS) C5(-/-) measured using fluorescent probes. Furthermore, lack colocalization p47(phox) protein NADPH oxidase (phox) complex GFP-expressing MTB (gfpMTB) indicated assembly phox on phagosomes. Reconstitution C5a, known ROS activator, enhanced phagosomes as well inhibited growth MTB. Protein kinase C (PKC) isoforms are involved phosphorylation translocation onto bacterial Western blot analysis demonstrated PKC (alpha, beta, delta) PKC-zeta cytosol compared C5 intact (C5(+/+)) situ labeling PKC-beta not phosphorylated Because Fc receptor-mediated normal both C5(+/+) macrophages, defect around specific deficiency. function thus appears due prevents effective