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CD11c(+)/CD11b(+) cells are critical for organic dust-elicited murine lung inflammation.
Poole-JA; Gleason-AM; Bauer-C; West-WW; Alexis-N; van Rooijen-N; Reynolds-SJ; Romberger-DJ; Kielian-TL
Am J Respir Cell Mol Biol 2012 Nov; 47(5):652-659
Organic dust exposure in the agricultural industry results in significant lung disease. Macrophage infiltrates are increased in the lungs after organic dust exposures, yet the phenotype and functional importance of these cells remain unclear. Using an established intranasal inhalation murine model of dust-induced lung inflammation, animals were treated once or daily for 3 weeks with swine confinement organic dust extract (DE). Repetitive DE treatment for 3 weeks resulted in significant increases in CD11c(+)/CD11b(+) macrophages in whole lung-associated tissue. These cells displayed increased costimulatory molecule (CD80 and CD86) expression, enhanced phagocytic ability, and an increased production of IL-6, CXCL1, and CXCL2. Similar findings were observed with the CD11c(+)/CD11b(+) macrophage infiltrate after repetitive exposure to peptidoglycan, a major DE component. To determine the functional importance of macrophages in mediating DE-induced airway inflammation, lung macrophages were selectively depleted using a well-established intranasal clodronate liposome depletion/suicide strategy. First, macrophage depletion by clodronate liposomes resulted in significant reductions in airway neutrophil influx and TNF-a and IL-6 production after a single exposure to DE. In contrast, after repetitive 3-week exposure to DE, airway lavage fluid and lung tissue neutrophils were significantly increased in clodronate liposome-treated mice compared with control mice. A histological examination of lung tissue demonstrated striking increases in alveolar and bronchiolar inflammation, as well as in the size and distribution of cellular aggregates in clodronate-liposome versus saline-liposome groups repetitively exposed to DE. These studies demonstrate that DE elicits activated CD11c(+)/CD11b(+) macrophages in the lung, which play a critical role in regulating the outcome of DE-induced airway inflammation.
Respiratory-system-disorders; Pulmonary-system-disorders; Lung-disorders; Lung-cells; Organic-dusts; Dust-exposure; Nasal-cavity; Inhalants; Inhalation-studies; Agriculture; Laboratory-animals; Laboratory-testing; Animal-husbandry; Animal-studies; Lung-irritants; Lung-tissue; Immune-reaction; Phagocytes; Neutrophils; Stimulants; Peptides; Antigens; Metabolism; Airway-resistance; Author Keywords: macrophage; neutrophil; airway inflammation; peptidoglycan; organic dust
Jill A. Poole, M.D., Pulmonary, Critical Care, Sleep, and Allergy Division, Department of Medicine, University of Nebraska Medical Center, 985300 The Nebraska Medical Center, Omaha, NE 68198-5300
Grant; Cooperative Agreement; Agriculture
Issue of Publication
Agriculture, Forestry and Fishing
American Journal of Respiratory Cell and Molecular Biology
NE; NC; CO
University of Nebraska Medical Center, Omaha, Nebraska
Page last reviewed: September 2, 2020
Content source: National Institute for Occupational Safety and Health Education and Information Division