Enhanced human IgE production results from exposure to the aromatic hydrocarbons from diesel exhaust: Direct effects on B-cell IgE production,☆☆,,★★

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Abstract

Epidemiologic and experimental studies suggest that air pollution, and particularly diesel exhaust particles (DEPs) may play a role in the increasing prevalence and severity of airway allergic disease. We show that the extract of polyaromatic hydrocarbons (PAHs) from DEPs (PAH-DEP) enhances human IgE production from purified B cells. Interleukin-4 plus CD40 monoclonal antibody–stimulated IgE production was enhanced 20% to 360% by the addition of PAH-DEP over a period of 10 to 14 days. This effect was increased when PAH-DEP was added 2 to 5 days after cultures were initiated. PAH-DEP itself did not induce IgE production or synergize with interleukin-4 alone to induce IgE from purified B cells, suggesting that it was enhancing ongoing IgE production rather than inducing germline transcription or isotype switching. The prototype nonmetabolized aromatic hydrocarbon 2,3,7,8 tetracholorodibenzo-p-dioxin, which functions solely through activation of the cytosolic aromatic hydrocarbon receptor complex, also increased IgE production. Additionally, the pattern of mRNAs coding for distinct isoforms of the ϵ chain was altered by PAH-DEP, and B-cell expression of the low-affinity IgE receptor was upregulated by PAH-DEP. Enhanced IgE production in the human airway, resulting from exposure to PAH-DEP, may be an important factor in the increase in airway allergic disease. (J ALLERGY CLIN IMMUNOL 1995;95:103-115)

Section snippets

Cell preparation and culture conditions

PBMCs were obtained from healthy donors between the ages of 21 and 48 years. Tonsil cells were obtained from specimens removed at surgery, and single cell suspensions were prepared. Mononuclear cells were obtained by density-gradient centrifugation with Lymphoprep (Nycomed Pharma, Oslo, Norway; 1077 kg/m3). For complete T cell removal, two cycles of 2-aminoethylisothiouronium bromide hydrobromide (Sigma Chemical Co., St. Louis, Mo.) treated sheep red cell rosette formation and depletion were

PAH-DEP enhances IgE production induced by IL-4/CD40

We tested the ability of PAH-DEP to induce human IgE production. When added alone over a dose range of 0.005 to 500 ng/ml, PAH did not induce de novo IgE production from either PBMCs or purified human B cells. Similarly, PAH-DEP was unable to induce IgE production from PBMCs or purified human B cells in the presence of CD40 mAb. When purified B cells were treated with IL-4 to induce ϵ germline transcription,28 addition of PAH-DEP still did not lead to the appearance of IgE protein in the

DISCUSSION

In this report we demonstrate that PAH-DEP enhances the production of IgE from human B cells. Production of IgE from human cells involves a number of distinct steps: (1) induction of ϵ germline transcription, (2) DNA recombination (isotype switching), (3) RNA transcription, (4) RNA splicing, and (5) translation of the mature mRNA into protein.20, 28, 31, 32 PAH-DEP–enhanced IgE production was not attributable to induction of germline transcription or isotype switching. PAH-DEP was unable to

Acknowledgements

We thank Drs. Eugene Medlock and Larry Sousa of Amgen, Inc. (Thousand Oaks, Calif.) for the generous gift of recombinant IL-4 and Dr. Ed A. Clark of the University of Washington, Seattle, Washington, for the kind gift of anti-CD40 mAb G28-5.

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  • Cited by (0)

    From aThe Hart and Louise Lyon Laboratory, Division of Clinical Immunology/Allergy, Department of Medicine; bThe Molecular Biology Institute; and cThe Jonsson Comprehensive Cancer Center, UCLA School of Medicine, University of California, Los Angeles.

    ☆☆

    Supported by United States Public Health Service grants AI-15251 and AI-34567 (UCLA Asthma, Allergy and Immunologic Disease Center), and gifts from the Asthma Research Foundation and the Dorothy Fund. David Diaz-Sanchez is the recipient of the McClure Foundation Fellowship from the Los Angeles Chapter of the Asthma and Allergy Foundation.

    Reprint requests: Andrew Saxon, MD, Division of Clinical Immunology/Allergy, Department of Medicine, 52-175 Center for Health Sciences, UCLA School of Medicine, Los Angeles, CA 90024-1680.

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