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 part icles (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 enviro nment, and even promote primary allergic sensitization. Experiments suggest that these effects result from the initial activation of mast cells to pro duce IL-4. Objective: We sought to demonstrate that in vivo mast cell activation by DE Ps plus allergen will also affect the release of classic mast cell mediator s and consequently enhance the immediate-phase response. Methods: Dust mite-sensitive subjects were challenged intranasally with all ergen, and symptom scores and histamine levels in nasal wash samples were c ompared 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 intrana sal dust mite allergen was required to induce clinical symptoms. DEPs alone had no effect. The changes in symptoms correlated with histamine levels me asured in nasal lavage specimens from these subjects, Although challenge wi th DEPs alone did not induce histamine release, challenge with both DEPs an d allergen resulted in 3-fold higher histamine concentrations than those se en with allergen alone. In contrast, carbon black particles (elemental carb on devoid of chemicals) had no effect. The role of chemicals was confirmed because degranulation of a murine mast cell fine by Fc epsilon RI cross-lin king was increased significantly (by 72%) by the soluble organic chemicals extracted from DEPs. Conclusions: Overall, these results suggest that exposure to DEPs can enhan ce the severity of clinical symptoms to allergen by enhancing mast cell deg ranulation.