Modulation of polymorphonuclear cell interleukin-8 secretion by human monoclonal antibodies to type 8 pneumococcal capsular polysaccharide

Infect Immun. 2003 Dec;71(12):6775-83. doi: 10.1128/IAI.71.12.6775-6783.2003.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Bacterial / chemistry
  • Antibodies, Bacterial / immunology
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / immunology*
  • Antibody Specificity
  • Coculture Techniques
  • Gene Expression Regulation
  • Immunoglobulin A / chemistry
  • Immunoglobulin A / genetics
  • Immunoglobulin A / immunology
  • Immunoglobulin Isotypes / chemistry
  • Immunoglobulin Isotypes / genetics
  • Immunoglobulin Isotypes / immunology
  • Immunoglobulin M / immunology
  • Interleukin-8 / metabolism*
  • Mice
  • Molecular Sequence Data
  • Neutrophils / immunology*
  • Opsonin Proteins
  • Phagocytosis
  • Pneumococcal Infections / prevention & control
  • Polysaccharides, Bacterial / immunology*
  • Streptococcus pneumoniae / classification
  • Streptococcus pneumoniae / growth & development
  • Streptococcus pneumoniae / immunology*

Substances

  • Antibodies, Bacterial
  • Antibodies, Monoclonal
  • Immunoglobulin A
  • Immunoglobulin Isotypes
  • Immunoglobulin M
  • Interleukin-8
  • Opsonin Proteins
  • Polysaccharides, Bacterial
  • pneumococcal polysaccharide, type 8

Associated data

  • GENBANK/AF332144
  • GENBANK/AF332145