title: CD11c(+)/CD11b(+) cells are critical for organic dust-elicited murine lung inflammation.
abstract: 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-α 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.
authors: Pulmonary, Critical Care, Sleep, and Allergy Division, Department of Medicine, University of Nebraska Medical Center, 985300 The Nebraska Medical Center, Omaha, NE 68198-5300, USA. japoole@unmc.edu
authors: Jill A
authors: JA
authors: Poole
authors: Angela M
authors: AM
authors: Gleason
authors: Christopher
authors: C
authors: Bauer
authors: William W
authors: WW
authors: West
authors: Neil
authors: N
authors: Alexis
authors: Nico
authors: N
authors: van Rooijen
authors: Stephen J
authors: SJ
authors: Reynolds
authors: Debra J
authors: DJ
authors: Romberger
authors: Tammy L
authors: TL
authors: Kielian
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism*; D039521:CD11c Antigen / Q000378:metabolism*; D004002:Clodronic Acid / Q000008:administration & dosage; D004391:Dust / Q000276:immunology*; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008081:Liposomes; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration; D010457:Peptidoglycan / Q000276:immunology*; D010587:Phagocytosis; D011014:Pneumonia / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D013211:Staphylococcus aureus / Q000276:immunology; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000485:Allergens; D039481:CD11b Antigen; D039521:CD11c Antigen; D004391:Dust; D018836:Inflammation Mediators; D015850:Interleukin-6; D008081:Liposomes; D010457:Peptidoglycan; D014409:Tumor Necrosis Factor-alpha; D004002:Clodronic Acid