Modulation of Polymorphonuclear Cell Interleukin-8 Secretion by Human Monoclonal Antibodies to Type 8 Pneumococcal Capsular Polysaccharide

Tamika Burns, Zhaojing Zhong, Michael Steinitz, Liise-anne Pirofski

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)6775-6783
Number of pages9
JournalInfection and Immunity
Volume71
Issue number12
DOIs
StatePublished - Dec 2003

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Interleukin-8
Streptococcus pneumoniae
Monoclonal Antibodies
Immunoglobulin M
Immunoglobulin A
Coculture Techniques
Polysaccharides
Interleukin-6
Immunoglobulin G
Classical Complement Pathway
Pneumococcal Vaccines
Trypan Blue
NAD
type 8 pneumococcal polysaccharide
Enzyme-Linked Immunosorbent Assay
Staining and Labeling
Infection

ASJC Scopus subject areas

  • Immunology

Cite this

Modulation of Polymorphonuclear Cell Interleukin-8 Secretion by Human Monoclonal Antibodies to Type 8 Pneumococcal Capsular Polysaccharide. / Burns, Tamika; Zhong, Zhaojing; Steinitz, Michael; Pirofski, Liise-anne.

In: Infection and Immunity, Vol. 71, No. 12, 12.2003, p. 6775-6783.

Research output: Contribution to journalArticle

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