title: Modulation of polymorphonuclear cell interleukin-8 secretion by human monoclonal antibodies to type 8 pneumococcal capsular polysaccharide.
abstract: Pneumococcal capsular polysaccharide (PS) vaccines induce type-specific immunoglobulin M (IgM), IgG, and IgA. Type-specific IgG to the PS is sufficient to confer protection against the homologous serotype of the pneumococcus, but the efficacies of type-specific IgM and IgA are less well understood. We examined the in vitro activities and efficacies in mice of two human monoclonal antibodies (MAbs) to type 8 PS, NAD (IgA) and D11 (IgM). MAb-mediated opsonophagocytic killing was evaluated after coculture of type 8 pneumococci with human polymorphonuclear cells (PMNs), type-specific or control MAbs, and human complement sources. The effects of the MAbs on PMN interleukin-8 (IL-8) and IL-6 secretion were determined in supernatants from cocultures containing pneumococci and PMNs by enzyme-linked immunosorbent assay. MAb efficacy was determined in an intratracheal model of type 8 infection in mice with classical complement pathway deficiency. Both MAbs were protective in 100% of infected mice. Neither MAb promoted a significant amount of killing of type 8 pneumococci compared to its isotype control MAb. Both type-specific MAbs mediated complement-dependent modulation of PMN IL-8 secretion, with increased secretion at effector/target (E:T) ratios of 500:1 and 50:1 and reduced secretion at 1:5. Trypan blue staining revealed that PMNs cocultured with D11 were less viable at an E:T ratio of 1:5 than PMNs cocultured with the control MAb. PMN IL-6 secretion was increased by both type-specific and control MAbs. These results suggest that certain type-specific IgM and IgAs might contribute to host defense by modulation of the inflammatory response to pneumococci.
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Tamika
authors.initials: T
authors.lastname: Burns
authors.forename: Zhaojing
authors.initials: Z
authors.lastname: Zhong
authors.forename: Michael
authors.initials: M
authors.lastname: Steinitz
authors.forename: Liise-anne
authors.initials: LA
authors.lastname: Pirofski
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000737:chemistry / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology*; D000918:Antibody Specificity; D018920:Coculture Techniques; D005786:Gene Expression Regulation; D007070:Immunoglobulin A / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D007132:Immunoglobulin Isotypes / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D016209:Interleukin-8 / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000276:immunology*; D009895:Opsonin Proteins; D010587:Phagocytosis; D011008:Pneumococcal Infections / Q000517:prevention & control; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000145:classification / Q000254:growth & development / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D007070:Immunoglobulin A; D007132:Immunoglobulin Isotypes; D007075:Immunoglobulin M; D016209:Interleukin-8; D009895:Opsonin Proteins; D011135:Polysaccharides, Bacterial; C121798:pneumococcal polysaccharide, type 8