Combined diesel exhaust particulate and ragweed allergen challenge markedly enhances human in vivo nasal ragweed-specific IgE and skews cytokine production to a T helper cell 2-type pattern.
We have previously shown that in vivo nasal challenge with diesel exhaust particles (DEP) induces both quantitative and qualitative changes in local IgE production and stimulates generalized local cytokine production. We have now investigated the combined effects of intranasal challenge with DEP plus ragweed allergen on local humoral immune responses. We collected nasal lavages from ragweed sensitized subjects at different times after nasal challenge. As compared with challenge with ragweed alone, challenge with both DEP and ragweed induced markedly higher ragweed-specific IgE but not total IgE levels or IgE-secreting cell numbers. Total and specific IgG4 levels also were enhanced, while total IgG levels were not. Synergy was also observed between the DEP and ragweed in altering the profile of epsilon mRNAs generated by alternative splicing, mRNAs that code for different expressed IgE proteins. Intranasal challenge with ragweed alone induced inconsistent and low levels of mucosal cytokine mRNAs. In contrast, challenge with both ragweed plus DEP resulted in decreased expression for Th1-type cytokines (IFN-gamma and IL-2) but elevated expression of mRNA for other cytokines (IL-4, -5, IL-6, IL-10, IL-13). This synergy between DEP and natural allergen exposure is suggested as a key feature in increasing allergen-induced respiratory allergic disease.
Diaz-Sanchez
D
D
Hart and Louise Lyon Laboratory, University of California Los Angeles School of Medicine 90024, USA. ddiazsa@ucla.edu
Tsien
A
A
Fleming
J
J
Saxon
A
A
D000328:Adult; D000485:Allergens / Q000008:administration & dosage* / Q000276:immunology; D000918:Antibody Specificity / Q000187:drug effects; D000921:Antibody-Producing Cells / Q000378:metabolism; D052179:Antigens, Plant; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000235:genetics; D007139:Immunoglobulin epsilon-Chains / Q000096:biosynthesis / Q000235:genetics; D007136:Immunoglobulins / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000276:immunology* / Q000378:metabolism; D009299:Nasal Provocation Tests; D010940:Plant Proteins / Q000008:administration & dosage*; D006109:Poaceae / Q000276:immunology; D011083:Polycyclic Compounds / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000096:biosynthesis; D018418:Th2 Cells / Q000378:metabolism*; D001335:Vehicle Emissions
D000485:Allergens; C026967:Amb a I protein, Ambrosia artemisiifolia; D052179:Antigens, Plant; D016207:Cytokines; D007070:Immunoglobulin A; D007139:Immunoglobulin epsilon-Chains; D007136:Immunoglobulins; D010940:Plant Proteins; D011083:Polycyclic Compounds; D012333:RNA, Messenger; D001335:Vehicle Emissions; D007073:Immunoglobulin E