title: Availability of complement bound to Staphylococcus aureus to interact with membrane complement receptors influences efficiency of phagocytosis.
abstract: Complement-mediated opsonization of encapsulated Staphylococcus aureus (CP+) of the predominant capsule types, 5 and 8, remains poorly understood. Our previous work showed that complement is important for mouse survival of CP+ type 5 bacteremia and that the type 5 capsule inhibits the binding of opsonic C3 fragments to the organism. The importance of complement-mediated opsonization of CP+ was tested by neutrophil phagocytosis assays. Complement-mediated opsonization of CP+ increased phagocytosis by 57% compared to opsonization in complement-inhibited serum. Agar-grown CP+, enhancing capsule expression, was phagocytosed only one-tenth as well as the capsule-negative organisms (CP-), supporting the belief that staphylococcal polysaccharide capsules impair phagocytosis. Despite relatively poor phagocytosis of CP+ compared to CP-, complement activation increased the phagocytosis of CP+ by 103%. Thus, complement in normal human serum may have an important role in opsonizing CP+, even when capsule expression is strong. The ability of bound C3 fragments to interact with complement receptor 1 (CD35) on the membrane of human erythrocytes was tested in an immune adherence assay. S. aureus capsule was able to mask C3 fragments on the organism from binding to complement receptor 1. The inhibition of C3 binding to CP+ and the masking of deposited C3 fragments caused by the presence of capsule was associated with markedly decreased phagocytosis. The addition of anti-capsule antibodies to normal human serum was found to markedly improve the recognition of deposited C3 fragments by complement receptor 1 even when the absolute number of C3 molecules bound to S. aureus was not increased.
authors.affiliation: Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710, USA. cunniok@chkd.org
authors.forename: K M
authors.initials: KM
authors.lastname: Cunnion
authors.forename: H-M
authors.initials: HM
authors.lastname: Zhang
authors.forename: M M
authors.initials: MM
authors.lastname: Frank
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D016667:Bacterial Capsules / Q000378:metabolism*; D003176:Complement C3 / Q000378:metabolism*; D004912:Erythrocytes / Q000276:immunology; D006801:Humans; D009504:Neutrophils / Q000276:immunology; D009895:Opsonin Proteins; D010587:Phagocytosis; D011951:Receptors, Complement / Q000378:metabolism*; D017463:Receptors, Complement 3b / Q000276:immunology / Q000378:metabolism; D013211:Staphylococcus aureus / Q000254:growth & development / Q000276:immunology* / Q000378:metabolism
chemical_list: D000907:Antibodies, Bacterial; D003176:Complement C3; D009895:Opsonin Proteins; D011951:Receptors, Complement; D017463:Receptors, Complement 3b