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 fine by Fc epsilon RI 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.