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Abstract

Coagulase-negative staphylococci (CoNS) are commonly associated with infections of prosthetic devices mediated by adsorbed host factors on biomaterial surfaces. Complement activation is known to occur and induce unspecific inflammation around the biomaterials. Human vitronectin (Vn) and clusterin (Clu), two potent inhibitors of complement, can be bound by CoNS. With a hypothesis whether binding of Vn or Clu influences complement activation, two measurements were determined. For Vn, complement activation was measured with a mouse anti-activated human C9 antibody. In the presence of Vn-binding strain, Staphylococcus hemolyticus SM13I, complement activation on a surface pre-coated with Vn occurred as it did in the absence of Vn pre-coating. For S. epidermidis 3380, which does not express binding of Vn, complement activation on a Vn-presented surface was significantly decreased. For Clu, erythrocytes lysis was measured to reflect the end product of complement activation (membrane attack complex). The complement-induced hemolysis increased when human serum was pre-incubated with Clu-binding strains, S. epidermidis J9P. The enhancement of hemolysis by J9P decreased when serum was supplemented by exogenous Clu. The data imply that interaction between CoNS and Vn or Clu interferes with one of their physiological functions, complement inhibition.

The Emerging Roles of Extracellular Chaperones in Complement Regulation

“…The binding of CLU to bacteria and/or bacterial components may inhibit MAC formation. The binding of CLU to the Streptococcus pyogenes virulence protein SIC [ 77 ], the dengue virus non-structural protein 1 [ 78 ] and the Pseudomonas aeruginosa protein dihydrolipoamide dehydrogenase [ 79 ] has been reported to inhibit complement activation and MAC formation, whilst the binding of CLU to Staphylococci epidermis J9P was reported to enhance complement-induced bacterial lysis [ 80 ]. CLU was also shown to co-localise with MAC in myocardial infarction [ 81 ].…”

Understanding and Designing of Bent Aromatic Heterometallabenzenes

“… Previous studies have demonstrated that the introduction of heteroatoms on the benzene ring can often endow the compounds with unique properties and broaden their applications. − For example, pyridine and pyrimidine with nitrogen atoms embedded in the conjugated rings have been widely used in biopharmaceuticals. , Besides, chlorophylls play essential roles in harvesting and transferring the solar energy for splitting water and generating oxygen. , At the same time, heme is responsible for transporting oxygen in the human body . Nitrogen-containing metalloporphyrins have also been synthesized for catalysis, photochemistry, and biopharmaceutical applications. − Considering the great potential of heterobenzenes in practical applications, it is valuable to devote efforts to extending the investigations on heterometallabenzenes as the simultaneous presence of metal atom and heteroatom in the benzene ring could result in more intriguing properties.…”