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

• Published in: Journal of allergy and clinical immunology 2006-06, Vol.117 (6), p.1396-1403
• Main Authors: Alexis, Neil E., Lay, John C., Zeman, Kirby, Bennett, William E., Peden, David B., Soukup, Joleen M., Devlin, Robert B., Becker, Susanne
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aerosols; Air Pollutants - immunology; Air Pollutants - pharmacology; airway macrophages; Asthma; Biological and medical sciences; Bronchi - cytology; Bronchi - immunology; Bronchi - metabolism; Chronic obstructive pulmonary disease; Disease; eotaxin; Female; Fractions; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunopathology; Immunophenotyping; Inhalation Exposure; Macrophage Activation - immunology; Male; mCD14; Medical sciences; Neutrophil Activation - immunology; Particle Size; Phagocytosis - immunology; PM 2.5-10; Respiratory Mucosa - cytology; Respiratory Mucosa - immunology; Sputum - cytology; Sputum - immunology; Sputum - metabolism; Studies; TNF-α
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2006.02.030

In vitro, endotoxin on coarse fraction particulate matter (PM 2.5-10) accounts for the majority of the ability of PM 2.5-10 to induce cytokine responses from alveolar macrophages. We examined in vivo whether inhaled PM 2.5-10 from local ambient air induce inflammatory and immune responses in the airways of healthy human beings and whether biologic material on PM 2.5-10 accounts for these effects. On 3 separate visits, 9 healthy subjects inhaled nebulized saline (0.9%, control), PM 2.5-10 collected from local ambient air that was heated to inactivate biological material (PM 2.5-10 −), or nonheated PM (PM 2.5-10 +). PM 2.5-10 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. Inhaled PM 2.5-10 + 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 PM 2.5-10 (PM 2.5-10 −) had no effect on neutrophilia but significantly ( P < .05) attenuated mRNA TNF-α, eotaxin levels, cell surface marker responses, and phagocytosis. Biological components of PM 2.5-10 are not necessary to induce neutrophil responses but are essential in mediating macrophage responses. The ability of PM 2.5-10 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. PM 2.5-10 might enhance the response of individuals with allergy to airborne bacteria.