This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Al-Darmaki, S.
Right arrow Articles by Barbour, S. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Al-Darmaki, S.
Right arrow Articles by Barbour, S. E.

 Previous Article  |  Next Article 

Clinical and Diagnostic Laboratory Immunology, July 2004, p. 720-728, Vol. 11, No. 4
1071-412X/04/$08.00+0     DOI: 10.1128/CDLI.11.4.720-728.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Delineation of the Role of Platelet-Activating Factor in the Immunoglobulin G2 Antibody Response

Salma Al-Darmaki,{dagger} Kandi Knightshead,{dagger} Yuichi Ishihara,{ddagger} Al Best, Harvey A. Schenkein, John G. Tew, and Suzanne E. Barbour*

Clinical Research Center for Periodontal Diseases, Virginia Commonwealth University, Richmond, Virginia

Received 22 December 2003/ Returned for modification 16 March 2004/ Accepted 1 May 2004

Localized aggressive periodontitis (LAgP) is a chronic inflammatory disease characterized by severe destruction of periodontal tissues surrounding the first molars and incisors. LAgP subjects produce large amounts of immunoglobulin G2 (IgG2) antibody against oral pathogens, and this response is inversely correlated with the severity of disease. We previously demonstrated that platelet-activating factor (PAF) is required for optimal IgG2 responses. The present investigation was designed to determine the mechanism of IgG2 induction by PAF. Exogenous PAF acetylhydrolase suppressed approximately 80% of pokeweed mitogen-stimulated IgG2 production, confirming that PAF is essential for optimal responses. PAF-activated leukocytes produced gamma interferon (IFN-{gamma}), a Th1 cytokine that has been associated with IgG2 responses in previous studies. The monocyte-derived cytokines interleukin-12 (IL-12) and IL-18 are upstream of IFN-{gamma} production, and IgG2 production was suppressed by neutralizing antibodies against these proteins. In addition, PAF induced monocyte-derived dendritic cells (DC) but not macrophages (M{Phi}) to secrete IL-12 and IL-18. This observation was interesting because monocyte differentiation in LAgP subjects is skewed to the DC phenotype. Although other investigators have implicated IFN-{gamma} in IgG2 production, its precise role in this response is controversial. Our studies suggest that IFN-{gamma} induces isotype switching to IgG2 but only in concert with the Th2 cytokine IL-4. Thus, it appears that the unique PAF metabolism of LAgP monocytes or DC promotes Th1 responses that are essential for optimal IgG2 antibody production. As IgG2 antibodies opsonize oral bacteria and promote their clearance and destruction, these alterations in PAF metabolism may be essential for limiting disease severity in LAgP patients.

* Corresponding author. Present address: Department of Biochemistry, Virginia Commonwealth University, Box 980614, Richmond, VA 23298-0614. Phone: (804) 828-2308. Fax: (804) 828-1473. E-mail: sbarbour{at}hsc.vcu.edu.

{dagger} S.A.-D. and K.K. contributed equally to the work described in this report.

{ddagger} Present address: Department of Periodontology, School of Dentistry, Aichi-Gakuin University, Chikusa-ku, Nagoya 464-8651, Japan.

Clinical and Diagnostic Laboratory Immunology, July 2004, p. 720-728, Vol. 11, No. 4
1071-412X/04/$08.00+0     DOI: 10.1128/CDLI.11.4.720-728.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»