Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0348321 (Haemophilus)
 15,372 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous in vivo studies demonstrated that clearance of encapsulated Haemophilus influenzae from blood is associated with the deposition of C3 on these bacteria and is independent of the later complement components (C5-C9). Since clearance of encapsulated bacteria is determined by phagocytosis of bacteria by fixed tissue macrophages, we studied the interaction of H. influenzae type b with macrophages in vitro. Organisms bound to macrophages in the presence of nonimmune serum. Binding was not evident in heat-treated serum or in serum from complement depleted animals and was inhibited by F(ab')2 fragments of antibody to C3 and by blockade of the macrophage complement receptor type 3. The majority of organisms bound in the presence of complement alone remained extracellular. Antibody in the form of convalescent serum or an IgG1 monoclonal to type b capsule did not increase the total number of organisms associated with macrophages, but did increase the number of organisms ingested. Furthermore, complement enhanced antibody-mediated ingestion. This in vitro study demonstrates that complement largely mediates binding of H. influenzae to macrophages. This binding may be critical in determining the early clearance of these bacteria from blood and may be an important mechanism of defense in the nonimmune, as well as the immune host.
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PMID:Role of complement in mouse macrophage binding of Haemophilus influenzae type b. 229 97

Amplification of the Cap b locus of Haemophilus influenzae occurs frequently in clinical isolates and has been proposed to be a mechanism by which this organism evades host defense. To determine if amplification of this locus affected complement fixation, in vitro studies to determine complement-mediated bacteriolysis and complement-mediated opsonization of an isogenic set of organisms containing 2, 3, and 4 copies of the Cap b locus were performed. Organisms containing 4 copies of the Cap b locus were significantly more resistant to antibody-dependent, classical complement pathway-directed bacteriolysis than were organisms containing 2 copies. Organisms containing 3 copies of this locus exhibited intermediate susceptibility to lysis. Complement-mediated opsonization of these organisms was assessed by determining the degree of binding of bacteria to murine or human macrophages or to nonphagocytic cells transfected with the genes for human Mac-1, the complement receptor type 3. In all three assay systems, organisms containing 4 copies of the Cap b locus bound less well than did organisms containing 2 copies of this locus. Consistent with their decreased susceptibility to lysis and opsonization, organisms with 4 copies of the Cap b locus fixed less C3 than did organisms containing 2 copies. These data demonstrate that amplification of the Cap b locus is associated with decreased susceptibility to complement-mediated lysis and decreased complement-mediated opsonization and suggest that amplification is used by these pathogens to increase their resistance to complement-dependent host defense mechanisms [correction of mecanisms].
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PMID:Effect of amplification of the Cap b locus on complement-mediated bacteriolysis and opsonization of type b Haemophilus influenzae. 889 Feb 38

Pulmonary surfactant protein A (SP-A), a member of the collectin family, plays an important role in innate immune defense of the lung. In this study, we examined the role of SP-A in modulating complement receptor-mediated phagocytosis. Complement receptors (CR), CR3 (CD11b), and CR4 (CD11c) were expressed at reduced levels on the surface of alveolar macrophages from Sp-a(-/-) compared with Sp-a(+/+) mice. Administration of intratracheal SP-A to Sp-a(-/-) mice induced the translocation of CR3 from alveolar macrophage intracellular pools to the cell surface. Intratracheal challenge with Haemophilus influenza enhanced CR3 expression on the surface of alveolar macrophages from Sp-a(-/-) and Sp-a(+/+) mice, but relative expression remained lower in the Sp-a(-/-) mice at all time points post-inoculation. The effects of SP-A on macrophage and neutrophil CR3 redistribution between intracellular and cell surface pools were restricted to cells isolated from the lung. SP-A augmented CR3-mediated phagocytosis in a manner that was attenuated by N-glycanase or collagenase treatment of SP-A, implicating the N-linked sugar and collagen-like domains in that function. The binding of CR3 to SP-A was calcium dependent and mediated by the I-domain of CR3 and to a lesser extent by the CR3 lectin domain. Mapping of the domains of SP-A that were required for optimal binding to CR3 revealed that the N-linked sugars were more critical than the collagen-like domain or the extent of oligomeric assembly. We conclude that SP-A modulates the cell surface expression of CR3 on alveolar macrophages, binds to CR3, and enhances CR3-mediated phagocytosis.
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PMID:Surfactant protein A modulates cell surface expression of CR3 on alveolar macrophages and enhances CR3-mediated phagocytosis. 1915 16