title: ATP-binding cassette transporter 1 attenuates ovalbumin-induced neutrophilic airway inflammation.
abstract: Apolipoprotein A-I (apoA-I) is an important component of high-density lipoprotein particles that mediates reverse cholesterol transport out of cells by interacting with the ATP-binding cassette transporter 1 (ABCA1). apoA-I has also been shown to attenuate neutrophilic airway inflammation in experimental ovalbumin (OVA)-induced asthma by reducing the expression of granulocyte colony-stimulating factor (G-CSF). Here, we hypothesized that overexpression of the ABCA1 transporter might similarly attenuate OVA-induced neutrophilic airway inflammation. Tie2-human ABCA1 (hABCA1) mice expressing human ABCA1 under the control of the Tie2 promoter, which is primarily expressed by vascular endothelial cells, but can also be expressed by macrophages, received daily intranasal OVA challenges, 5 d/wk for 5 weeks. OVA-challenged Tie2-hABCA1 mice had significant reductions in total bronchoalveolar lavage fluid (BALF) cells that reflected a decrease in neutrophils, as well as reductions in peribronchial inflammation, OVA-specific IgE levels, and airway epithelial thickness. The reduced airway neutrophilia in OVA-challenged Tie2-hABCA1 mice was associated with significant decreases in G-CSF protein levels in pulmonary vascular endothelial cells, alveolar macrophages, and BALF. Intranasal administration of recombinant murine G-CSF to OVA-challenged Tie2-hABCA1 mice for 5 days increased BALF neutrophils to a level comparable to that of OVA-challenged wild-type mice. We conclude that ABCA1 suppresses OVA-induced airway neutrophilia by reducing G-CSF production by vascular endothelial cells and alveolar macrophages. These findings suggest that ABCA1 expressed by vascular endothelial cells and alveolar macrophages may play important roles in attenuating the severity of neutrophilic airway inflammation in asthma.
authors.affiliation: 1 Cardiovascular and Pulmonary Branch.
authors.forename: Cuilian
authors.initials: C
authors.lastname: Dai
authors.forename: Xianglan
authors.initials: X
authors.lastname: Yao
authors.forename: Boris
authors.initials: B
authors.lastname: Vaisman
authors.forename: Todd
authors.initials: T
authors.lastname: Brenner
authors.forename: Katharine S
authors.initials: KS
authors.lastname: Meyer
authors.forename: Meixia
authors.initials: M
authors.lastname: Gao
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Keeran
authors.forename: Gayle Z
authors.initials: GZ
authors.lastname: Nugent
authors.forename: Xuan
authors.initials: X
authors.lastname: Qu
authors.forename: Zu-Xi
authors.initials: ZX
authors.lastname: Yu
authors.forename: Pradeep K
authors.initials: PK
authors.lastname: Dagur
authors.forename: J Philip
authors.initials: JP
authors.lastname: McCoy
authors.forename: Alan T
authors.initials: AT
authors.lastname: Remaley
authors.forename: Stewart J
authors.initials: SJ
authors.lastname: Levine
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics* / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002784:Cholesterol / Q000276:immunology; D042783:Endothelial Cells / Q000276:immunology; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics; D006801:Humans; D016676:Macrophages, Alveolar / Q000276:immunology; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009504:Neutrophils / Q000276:immunology*; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D042787:Receptor, TIE-2 / Q000235:genetics
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D016179:Granulocyte Colony-Stimulating Factor; D010047:Ovalbumin; D002784:Cholesterol; D042787:Receptor, TIE-2; C079086:Tek protein, mouse
keywords: ATP-binding cassette transporter 1; airway inflammation; neutrophil; ovalbumin; vascular endothelial cells