Role of complement in mouse macrophage binding of Haemophilus influenzae type b.

Abstract

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.

The Role of C3 in Mediating Binding and Ingestion of Group B Streptococcus Serotype III by Murine Macrophages

“…C3-dependent binding may be important in determining mononuclear phagocyte-dependent clearance of these pathogens from blood, particularly in patients with little or no type-specific serum antibody. (Pediatr Res 30: 118-123,1991) Abbreviations CR3, complement receptor type 3 Ni-S, nonimmune serum Im-S, immune serum CoVF, cobra venom factor PB, phagocytosis buffer i.p., intraperitoneal HBSS, Hanks' balanced salt solution role with encapsulated pneumococci and Haemophilus influenzae has underscored that complement-mediated phagocytosis is important in defending against these pathogens (2)(3)(4)(5)(6). These studies are consistent with the hypothesis that clearance of complement-opsonized bacteria from the circulation by mononuclear phagocytes composing the reticuloendothelial system is essential in defending against bacteremia and in preventing disseminated infection.…”

“…Antibody M1/70 (25), was incubated with macrophage monolayers for 20 min before addition of bacteria. The concentration of antibody M 1/70 used has been shown to inhibit specifically C3bi opsonized particle binding to monolayers while inhibiting less than 10% of IgG or C3b opsonized particle binding (3,25 Directed against macrophage surface antigens enhanced deposition seen with antibody-containing ascites was a result of antibody's effect rather than any residual complement activity in this fluid.…”

Protection by Natural Human Immunoglobulin M Antibody to Meningococcal Serogroup B Capsular Polysaccharide in the Infant Rat Protection Assay Is Independent of Complement-Mediated Bacterial Lysis

“…Thus, alternatively, in infant rats, the macrophages of the peritoneum or mononuclear phagocyte system (13), rather than PMNL, might have been responsible for bacterial clearance. It is well recognized that Fc and especially C3 receptors on macrophages play a crucial role in the clearance of other well-opsonized encapsulated bacteria from the bloodstream (8,10,35,37,42) and even in the absence of opsonins, pattern recognition molecules, especially the class A scavenger receptor, mediate meningococcal uptake by human bone marrow culture-derived macrophages (36).…”

Two-Component Systems in Haemophilus influenzae : a Regulatory Role for ArcA in Serum Resistance

“…The molecular mechanism of complement-mediated killing of gram-negative bacteria is thought to involve serum complement component C3 (46) and the complement membrane attack complex (MAC) inserted into the bacterial outer membrane. The MAC causes a loss of inner membrane potential and inhibits inner membrane respiration (12), which is believed to cause cell death.…”