Biological material on inhaled coarse fraction particulate matter activates airway phagocytes in vivo in healthy volunteers

BackgroundIn vitro, endotoxin on coarse fraction particulate matter (PM2.5-10) accounts for the majority of the ability of PM2.5-10 to induce cytokine responses from alveolar macrophages.ObjectiveWe examined in vivo whether inhaled PM2.5-10 from local ambient air induce inflammatory and immune responses in the airways of healthy human beings and whether biologic material on PM2.5-10 accounts for these effects.MethodsOn 3 separate visits, 9 healthy subjects inhaled nebulized saline (0.9%, control), PM2.5-10 collected from local ambient air that was heated to inactivate biological material (PM2.5-10−), or nonheated PM (PM2.5-10+). PM2.5-10 deposition (∼0.65 mg/subject) targeted the bronchial airways (confirmed by using radiolabeled aerosol), and induced sputum was obtained 2 to 3 hours postinhalation for analysis of cellular and biochemical markers of inflammation and innate immune function.ResultsInhaled PM2.5-10+ induced elevated inflammation (% PMNs, macrophage mRNA TNF-α), increased eotaxin, upregulated immune surface phenotypes on macrophages (mCD14, CD11b, HLA-DR), and increased phagocytosis (monocytes) versus saline (P < .05). Biological inactivation of PM2.5-10 (PM2.5-10−) had no effect on neutrophilia but significantly (P < .05) attenuated mRNA TNF-α, eotaxin levels, cell surface marker responses, and phagocytosis.ConclusionBiological components of PM2.5-10 are not necessary to induce neutrophil responses but are essential in mediating macrophage responses. The ability of PM2.5-10 to activate monocytic cells and potentially skew the airways toward an allergic phenotype by enhancing eotaxin levels may enhance responses to allergens or bacteria in individuals with allergy.Clinical implicationsPM2.5-10 might enhance the response of individuals with allergy to airborne bacteria.