Eculizumab inhibits the terminal, lytic pathway of complement by blocking the activation of the complement protein C5 and shows remarkable clinical benefits in certain complement-mediated diseases. However, several reports suggest that activation of C5 is not always completely suppressed in patients even under excess of eculizumab over C5, indicating that residual C5 activity may derogate the d...

A unique experimental model is described, where natural immunologic tolerance to a well-defined soluble native antigen (murine C5) is examined in congenic strains of mice that differ only by the presence or the absence of C5. A highly sensitive hemolytic assay was developed to detect nanogram amounts of C5 as well as an assay of anti-C5 inhibition of C5 hemolytic activity. The latter was more s...

Experimental conditions required for the expression of maximum C5 activation upon limited trypsin hydrolysis were determined to be 0.008 mol of trypsin/mol C5 in a reaction mixture containing 1 mg C5/ml veronal-buffered saline incubated at 37 degrees C for 30 min. Employing these optimal incubation conditions, the primary or preferred site of trypsin hydrolysis of the C5 alpha-chain resulted in...

Leptospirosis is considered one of the most important zoonosis worldwide. The activation of the Complement System is important to control dissemination of several pathogens in the host. Only a few studies have employed murine models to investigate leptospiral infection and our aim in this work was to investigate the role of murine C5 during in vivo infection, comparing wild type C57BL/6 (B6 C5+...

Complement C5-deficient (C5(-/-)) macrophages derived from B.10 congenic mice were found to be defective in killing intracellular Mycobacterium tuberculosis (MTB). They were bacteriostatic after activation with IFN-gamma alone but bactericidal in the combined presence of IFN-gamma and C5-derived C5a anaphylatoxin that was deficient among these macrophages. Reduced killing correlated with a decr...

Congenic C5-deficient and C5-sufficient mice were infected with group B streptococci (GBS) to determine if the polymorphonuclear leukocyte (PMNL) chemoattractant C5a contributes to PMNL recruitment in GBS infection and if GBS C5a-ase reduces C5a-induced PMNL recruitment in vivo. PMNL accumulation was greater in the peritoneum and air spaces of C5-sufficient mice than in C5-deficient mice. Admin...

The sex-dependent differences in serum levels of complement components have been reported concerning C4 (1), C5 (2, 3), C6 (3), C4-binding protein (C4-bp) ~ (4), and sex-limited protein (Slp) (5) in the mouse complement system. The serum levels o f these components in adult mice are always higher in males than in females within each inbred strain and are strongly under hormonal control. With re...