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Infection and Immunity, December 2003, p. 6775-6783, Vol. 71, No. 12
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.12.6775-6783.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

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

Tamika Burns,1 Zhaojing Zhong,2 Michael Steinitz,3 and Liise-anne Pirofski1,2*

Department of Microbiology and Immunology, Albert Einstein College of Medicine,1 Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York,2 Experimental Pathology, The Hebrew University-Hadassah Medical School, Jerusalem, Israel3

Received 25 February 2003/ Returned for modification 1 April 2003/ Accepted 26 August 2003

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.

* Corresponding author. Mailing address: Division of Infectious Diseases, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461. Phone: (718) 430-2372. Fax: (718) 430-2292. E-mail: pirofski{at}aecom.yu.edu.

Editor: T. R. Kozel

Infection and Immunity, December 2003, p. 6775-6783, Vol. 71, No. 12
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.12.6775-6783.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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