Diesel exhaust particles directly induce activated mast cells to degranulate and increase histamine levels and symptom severity.
BACKGROUND
The ability of combustion products, such as diesel exhaust particles (DEPs), to modulate the immune system has now been firmly established. DEPs can synergize with allergen at the human upper respiratory mucosa to enhance allergen-specific IgE production, initiate a T(H)2 cytokine environment, and even promote primary allergic sensitization. Experiments suggest that these effects result from the initial activation of mast cells to produce IL-4.


OBJECTIVE
We sought to demonstrate that in vivo mast cell activation by DEPs plus allergen will also affect the release of classic mast cell mediators and consequently enhance the immediate-phase response.


METHODS
Dust mite-sensitive subjects were challenged intranasally with allergen, and symptom scores and histamine levels in nasal wash samples were compared after prechallenge with 0.3 mg of DEPs.


RESULTS
If the subjects were first sprayed with DEPs, mean symptom scores rose from 3.7 to 9.9; additionally, only one fifth of the amount of intranasal dust mite allergen was required to induce clinical symptoms. DEPs alone had no effect. The changes in symptoms correlated with histamine levels measured in nasal lavage specimens from these subjects. Although challenge with DEPs alone did not induce histamine release, challenge with both DEPs and allergen resulted in 3-fold higher histamine concentrations than those seen with allergen alone. In contrast, carbon black particles (elemental carbon devoid of chemicals) had no effect. The role of chemicals was confirmed because degranulation of a murine mast cell line by FcepsilonRI cross-linking was increased significantly (by 72%) by the soluble organic chemicals extracted from DEPs.


CONCLUSIONS
Overall, these results suggest that exposure to DEPs can enhance the severity of clinical symptoms to allergen by enhancing mast cell degranulation.
Diaz-Sanchez
D
D
Hart and Louise Lyon Laboratory, Division of Clinical Immunology/Allergy, Department of Medicine, UCLA School of Medicine, University of California, Los Angeles 90095-1680, USA.
Penichet-Garcia
M
M
Saxon
A
A
D000328:Adult; D000818:Animals; D015550:Cell Degranulation / Q000187:drug effects; D002460:Cell Line; D005260:Female; D006632:Histamine / Q000378:metabolism*; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000166:cytology*; D008875:Middle Aged; D009299:Nasal Provocation Tests; D012720:Severity of Illness Index; D001335:Vehicle Emissions
D001335:Vehicle Emissions; D006632:Histamine