The organic component of diesel exhaust particles and phenanthrene, a major polyaromatic hydrocarbon constituent, enhances IgE production by IgE-secreting EBV-transformed human B cells in vitro.
Suspended airborne particulate matter such as diesel exhaust particles (DEP) have been implicated in the increased incidence of respiratory allergic diseases that has occurred over the past century. Studies in vitro and in vivo have shown that DEP may enhance allergic antibody (IgE) expression. DEP contain a wide spectrum of polycyclic aromatic hydrocarbons (PAH) that have been reported to have direct effects on the immune system, including the modulation of IgE production using various human and murine cell populations. We investigated the effects of the organic extract of DEP (PAH-DEP) and particularly, phenanthrene, a major component of DEP, in vitro on IgE production by 2C4/F3, a human Epstein-Barr virus transformed isotype switched, IgE producing B cell line. Phenanthrene consistently enhanced 2C4/F3 IgE production two- to threefold. This in vitro enhancement was associated with an increased expression of total IgE mRNA. Furthermore, the pattern of mRNA's coding for distinct isoforms of the epsilon chain was altered by both DEP-PAH and phenanthrene. While phenanthrene increased the level of productive epsilon transcripts, it did not increase epsilon germ line transcription. These effects were not due to an alteration of the cell cycle. Unstimulated 2C4/F3 cells contained detectable mRNA for IL6, IL10, TNF-alpha, and interestingly IL4; however, addition of PAH-DEP or phenanthrene did not significantly alter the level of these cytokines and thus did not appear to account for our findings. Thus, we have used our in vitro model to dissect the mechanism of DEP-PAH on IgE production in postswitch IgE producing cells and shown that phenanthrene, an important component in DEP and other pollutants, can act in a similar manner.
Tsien
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A
Hart and Louise Lyon Laboratory, University of California Los Angeles School of Medicine 90024-1680, USA.
Diaz-Sanchez
D
D
Ma
J
J
Saxon
A
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D001402:B-Lymphocytes / Q000187:drug effects*; D002461:Cell Line, Transformed; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D007139:Immunoglobulin epsilon-Chains / Q000187:drug effects / Q000235:genetics; D008213:Lymphocyte Activation; D010616:Phenanthrenes / Q000633:toxicity*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D001335:Vehicle Emissions / Q000633:toxicity*
D016207:Cytokines; D007139:Immunoglobulin epsilon-Chains; D010616:Phenanthrenes; D012333:RNA, Messenger; D001335:Vehicle Emissions; D007073:Immunoglobulin E; C031181:phenanthrene