title: Absence of the cystic fibrosis transmembrane regulator (Cftr) from myeloid-derived cells slows resolution of inflammation and infection.
abstract: The absence or reduction of CFTR function causes CF and results in a pulmonary milieu characterized by bacterial colonization and unresolved inflammation. The ineffectiveness at controlling infection by species such as Pseudomonas aeruginosa suggests defects in innate immunity. Macrophages, neutrophils, and DCs have all been shown to express CFTR mRNA but at low levels, raising the question of whether CFTR has a functional role in these cells. Bone marrow transplants between CF and non-CF mice suggest that these cells are inherently different; we confirm this observation using conditional inactivation of Cftr in myeloid-derived cells. Mice lacking Cftr in myeloid cells overtly appear indistinguishable from non-CF mice until challenged with bacteria instilled into the lungs and airways, at which point, they display survival and inflammatory profiles intermediate in severity as compared with CF mice. These studies demonstrate that Cftr is involved directly in myeloid cell function and imply that these cells contribute to the pathophysiological phenotype of the CF lung.
authors.affiliation: Department of Pediatrics, Case Western Reserve University, Cleveland, OH 44106-4948, USA. tracey.bonfield@case.edu
authors.forename: T L
authors.initials: TL
authors.lastname: Bonfield
authors.forename: C A
authors.initials: CA
authors.lastname: Hodges
authors.forename: C U
authors.initials: CU
authors.lastname: Cotton
authors.forename: M L
authors.initials: ML
authors.lastname: Drumm
mesh_terms: D000818:Animals; D003550:Cystic Fibrosis / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000172:deficiency* / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D007249:Inflammation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000276:immunology*; D011552:Pseudomonas Infections / Q000276:immunology; D012141:Respiratory Tract Infections / Q000276:immunology*
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator