title: Lipopolysaccharide-induced lung injury is independent of serum vitamin D concentration.
abstract: Vitamin D deficiency is increasing in incidence around the world. Vitamin D, a fat-soluble vitamin, has documented effects on the innate and adaptive immune system, including macrophage and T regulatory (Treg) cell function. Since Treg cells are important in acute lung injury resolution, we hypothesized that vitamin D deficiency increases the severity of injury and delays injury resolution in lipopolysaccharide (LPS) induced acute lung injury. Vitamin D deficient mice were generated, using C57BL/6 mice, through diet modification and limited exposure to ultraviolet light. At 8 weeks of age, vitamin D deficient and sufficient mice received 2.5 g/kg of LPS or saline intratracheal. At 1 day, 3 days and 10 days, mice were anesthetized and lung elastance measured. Mice were euthanized and bronchoalveolar lavage fluid, lungs and serum were collected. Ex vivo neutrophil chemotaxis was evaluated, using neutrophils from vitamin D sufficient and deficient mice exposed to the chemoattractants, KC/CXCL1 and C5a, and to bronchoalveolar lavage fluid from LPS-exposed mice. We found no difference in the degree of lung injury. Leukocytes were mildly decreased in the bronchoalveolar fluid of vitamin D deficient mice at 1 day. Ex-vivo, neutrophils from vitamin D deficient mice showed impaired chemotaxis to KC but not to C5a. Vitamin D deficiency modestly impairs neutrophil chemotaxis; however, it does not affect lung injury or its resolution in an LPS model of acute lung injury.
authors.affiliation: Center for Lung Biology, Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Lindy S
authors.initials: LS
authors.lastname: Klaff
authors.forename: Sean E
authors.initials: SE
authors.lastname: Gill
authors.forename: Brent E
authors.initials: BE
authors.lastname: Wisse
authors.forename: Kristen
authors.initials: K
authors.lastname: Mittelsteadt
authors.forename: Gustavo
authors.initials: G
authors.lastname: Matute-Bello
authors.forename: Peter
authors.initials: P
authors.lastname: Chen
authors.forename: William A
authors.initials: WA
authors.lastname: Altemeier
mesh_terms: D000818:Animals; D001823:Body Composition; D002633:Chemotaxis; D005247:Feeding Behavior; D007249:Inflammation / Q000097:blood / Q000473:pathology; D008070:Lipopolysaccharides; D008168:Lung / Q000473:pathology; D055370:Lung Injury / Q000097:blood* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000473:pathology; D014807:Vitamin D / Q000097:blood*
chemical_list: D008070:Lipopolysaccharides; D014807:Vitamin D