title: Neutrophils play a critical role in development of LPS-induced airway disease.
abstract: We investigated the role of neutrophils in the development of endotoxin-induced airway disease via systemic neutrophil depletion of C3H/HeBFeJ mice and coincident inhalation challenge with lipopolysaccharide (LPS) over a 4-wk period. Mice were made neutropenic with intraperitoneal injections of neutrophil antiserum before and throughout the exposure period. Experimental conditions included LPS-exposed, antiserum-treated; LPS-exposed, control serum-treated; air-exposed, antiserum-treated; and air-exposed, control serum-treated groups. Physiological, biological, and morphological assessments were performed after a 4-wk exposure and again after a 4-wk recovery period. After the 4-wk exposure, LPS-induced inflammation of the lower airways was significantly attenuated in the neutropenic mice, although airway responsiveness (AR) to methacholine (MCh) remained unchanged. After the recovery period, LPS-exposed neutrophil-replete mice had increased AR to MCh when compared with the LPS-exposed neutropenic animals. Morphometric data indicate that the 4-wk exposure to LPS leads to a substantial expansion of the subepithelial area of the medium-sized airways (90-129 microm diameter) in nonneutropenic mice but not neutropenic mice, and this difference persisted even after the recovery period. Expression of bronchial epithelial and subepithelial transforming growth factor-beta1 (TGF-beta1) was diminished in the challenged neutropenic mice compared with the neutrophil-sufficient mice. These studies demonstrate that neutrophils play a critical role in the development of chronic LPS-induced airway disease.
authors.affiliation: Pulmonary and Critical Care Division, Department of Medicine, Duke University Medical Center and Veterans Affairs Medical Center, Durham, North Carolina 27710, USA. jsavov@acpub.duke.edu
authors.forename: Jordan D
authors.initials: JD
authors.lastname: Savov
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Gavett
authors.forename: David M
authors.initials: DM
authors.lastname: Brass
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Costa
authors.forename: David A
authors.initials: DA
authors.lastname: Schwartz
mesh_terms: D000818:Animals; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000503:physiopathology*; D004195:Disease Models, Animal; D004731:Endotoxins / Q000633:toxicity; D004926:Escherichia coli; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009504:Neutrophils / Q000473:pathology / Q000502:physiology*; D013997:Time Factors
chemical_list: D004731:Endotoxins; D008070:Lipopolysaccharides