title: Protection against inhaled oxidants through scavenging of oxidized lipids by macrophage receptors MARCO and SR-AI/II.
abstract: Alveolar macrophages (AMs) express the class A scavenger receptors (SRAs) macrophage receptor with collagenous structure (MARCO) and scavenger receptor AI/II (SRA-I/II), which recognize oxidized lipids and provide innate defense against inhaled pathogens and particles. Increased MARCO expression in lungs of ozone-resistant mice suggested an additional role protecting against inhaled oxidants. After ozone exposure, MARCO-/- mice showed greater lung injury than did MARCO+/+ mice. Ozone is known to generate oxidized, proinflammatory lipids in lung lining fluid, such as 5beta,6beta-epoxycholesterol (beta-epoxide) and 1-palmitoyl-2-(9'-oxo-nonanoyl)-glycerophosphocholine (PON-GPC). Intratracheal instillation of either lipid caused substantial neutrophil influx in MARCO-/- mice, but had no effect in MARCO+/+ mice. Normal AMs showed greater uptake in vitro of beta-epoxide compared with MARCO-/- AMs, consistent with SRA function in binding oxidized lipids. SR-AI/II-/- mice showed similar enhanced acute lung inflammation after beta-epoxide or another inhaled oxidant (aerosolized leachate of residual oil fly ash). In contrast, subacute ozone exposure did not enhance inflammation in SR-AI/II-/- versus SR-AI/II+/+ mice, reflecting increased AM expression of MARCO. These data identify what we believe to be a novel function for AM SRAs in decreasing pulmonary inflammation after oxidant inhalation by scavenging proinflammatory oxidized lipids from lung lining fluids.
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
authors.forename: Morten
authors.initials: M
authors.lastname: Dahl
authors.forename: Alison K
authors.initials: AK
authors.lastname: Bauer
authors.forename: Mohamed
authors.initials: M
authors.lastname: Arredouani
authors.forename: Raija
authors.initials: R
authors.lastname: Soininen
authors.forename: Karl
authors.initials: K
authors.lastname: Tryggvason
authors.forename: Steven R
authors.initials: SR
authors.lastname: Kleeberger
authors.forename: Lester
authors.initials: L
authors.lastname: Kobzik
mesh_terms: D000818:Animals; D002244:Carbon / Q000378:metabolism / Q000633:toxicity; D060729:Coal Ash; D004852:Epoxy Compounds / Q000378:metabolism / Q000633:toxicity; D001239:Inhalation; D050356:Lipid Metabolism; D008168:Lung / Q000187:drug effects / Q000276:immunology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D009504:Neutrophils / Q000276:immunology; D016877:Oxidants / Q000378:metabolism* / Q000633:toxicity; D010084:Oxidation-Reduction; D010126:Ozone / Q000378:metabolism* / Q000633:toxicity; D052638:Particulate Matter / Q000378:metabolism / Q000633:toxicity; D011014:Pneumonia / Q000235:genetics / Q000276:immunology*; D011971:Receptors, Immunologic / Q000235:genetics / Q000502:physiology*; D051117:Scavenger Receptors, Class A / Q000235:genetics / Q000502:physiology*
chemical_list: D060729:Coal Ash; D004852:Epoxy Compounds; C092228:Marco protein, mouse; D016877:Oxidants; D052638:Particulate Matter; D011971:Receptors, Immunologic; D051117:Scavenger Receptors, Class A; D010126:Ozone; D002244:Carbon