Protection against inhaled oxidants through scavenging of oxidized lipids by macrophage receptors MARCO and SR-AI/II
Copyright policy )Protection against inhaled oxidants through scavenging of oxidized lipids by macrophage receptors MARCO and SR-AI/II
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.
- University of Copenhagen Denmark
- National Institutes of Health United States
- University of Copenhagen Denmark
- Research Triangle Park Foundation United States
- Karolinska Institute Sweden
Scavenger Receptors, Neutrophils, Alveolar, Coal Ash, Mice, Ozone, Immunologic, Receptors, Macrophages, Alveolar, Animals, Receptors, Immunologic, Lung, Macrophages, Scavenger Receptors, Class A, Pneumonia, Lipid Metabolism, Oxidants, Carbon, Mice, Mutant Strains, Mutant Strains, Inhalation, Epoxy Compounds, Particulate Matter, Class A, Oxidation-Reduction
Scavenger Receptors, Neutrophils, Alveolar, Coal Ash, Mice, Ozone, Immunologic, Receptors, Macrophages, Alveolar, Animals, Receptors, Immunologic, Lung, Macrophages, Scavenger Receptors, Class A, Pneumonia, Lipid Metabolism, Oxidants, Carbon, Mice, Mutant Strains, Mutant Strains, Inhalation, Epoxy Compounds, Particulate Matter, Class A, Oxidation-Reduction
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