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Delineation of the role of platelet-activating factor in the immunoglobulin G2 antibody response.

Publication ,  Journal Article
Al-Darmaki, S; Knightshead, K; Ishihara, Y; Best, A; Schenkein, HA; Tew, JG; Barbour, SE
Published in: Clin Diagn Lab Immunol
July 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 (MPhi) 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.

Duke Scholars

Published In

Clin Diagn Lab Immunol

DOI

ISSN

1071-412X

Publication Date

July 2004

Volume

11

Issue

4

Start / End Page

720 / 728

Location

United States

Related Subject Headings

  • Reverse Transcriptase Polymerase Chain Reaction
  • Platelet Activating Factor
  • Periodontal Diseases
  • Microbiology
  • Macrophages
  • Lymphocyte Activation
  • Leukocytes
  • Interleukin-4
  • Interferon-gamma
  • In Vitro Techniques
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Al-Darmaki, S., Knightshead, K., Ishihara, Y., Best, A., Schenkein, H. A., Tew, J. G., & Barbour, S. E. (2004). Delineation of the role of platelet-activating factor in the immunoglobulin G2 antibody response. Clin Diagn Lab Immunol, 11(4), 720–728. https://doi.org/10.1128/CDLI.11.4.720-728.2004
Al-Darmaki, Salma, Kandi Knightshead, Yuichi Ishihara, Al Best, Harvey A. Schenkein, John G. Tew, and Suzanne E. Barbour. “Delineation of the role of platelet-activating factor in the immunoglobulin G2 antibody response.Clin Diagn Lab Immunol 11, no. 4 (July 2004): 720–28. https://doi.org/10.1128/CDLI.11.4.720-728.2004.
Al-Darmaki S, Knightshead K, Ishihara Y, Best A, Schenkein HA, Tew JG, et al. Delineation of the role of platelet-activating factor in the immunoglobulin G2 antibody response. Clin Diagn Lab Immunol. 2004 Jul;11(4):720–8.
Al-Darmaki, Salma, et al. “Delineation of the role of platelet-activating factor in the immunoglobulin G2 antibody response.Clin Diagn Lab Immunol, vol. 11, no. 4, July 2004, pp. 720–28. Pubmed, doi:10.1128/CDLI.11.4.720-728.2004.
Al-Darmaki S, Knightshead K, Ishihara Y, Best A, Schenkein HA, Tew JG, Barbour SE. Delineation of the role of platelet-activating factor in the immunoglobulin G2 antibody response. Clin Diagn Lab Immunol. 2004 Jul;11(4):720–728.

Published In

Clin Diagn Lab Immunol

DOI

ISSN

1071-412X

Publication Date

July 2004

Volume

11

Issue

4

Start / End Page

720 / 728

Location

United States

Related Subject Headings

  • Reverse Transcriptase Polymerase Chain Reaction
  • Platelet Activating Factor
  • Periodontal Diseases
  • Microbiology
  • Macrophages
  • Lymphocyte Activation
  • Leukocytes
  • Interleukin-4
  • Interferon-gamma
  • In Vitro Techniques