title: Cutting Edge: CLEC5A Mediates Macrophage Function and Chronic Obstructive Pulmonary Disease Pathologies.
abstract: Chronic obstructive pulmonary disease (COPD) is a devastating disease with no effective therapies. We investigated the role of the C-type lectin receptor, CLEC5A, in macrophage activation and pulmonary pathogenesis in a mouse model of COPD. We demonstrate that CLEC5A is expressed on alveolar macrophages in mice exposed long-term to cigarette smoke (CS), as well as in human smokers. We also show that CLEC5A-mediated activation of macrophages enhanced cytokine elaboration alone, as well as in combination with LPS or GM-CSF in CS-exposed mice. Furthermore, usingClec5a-deficient mice, we demonstrate that CS-induced macrophage responsiveness is mediated by CLEC5A, and CLEC5A is required for the development of inflammation, proinflammatory cytokine expression, and airspace enlargement. These findings suggest a novel mechanism that promotes airway inflammation and pathologies in response to CS exposure and identifies CLEC5A as a novel target for the therapeutic control of COPD pathogenesis.
authors.affiliation: Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267; and.
authors.forename: Brian W
authors.initials: BW
authors.lastname: Wortham
authors.affiliation: Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267; and.
authors.forename: Bryan L
authors.initials: BL
authors.lastname: Eppert
authors.affiliation: Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267; and.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Flury
authors.affiliation: Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267; and.
authors.forename: Sara Morgado
authors.initials: SM
authors.lastname: Garcia
authors.affiliation: Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267; and.
authors.forename: Walter R
authors.initials: WR
authors.lastname: Donica
authors.affiliation: Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267; and.
authors.forename: Andrew
authors.identifier: http://orcid.org/0000-0003-3018-9134
authors.initials: A
authors.lastname: Osterburg
authors.affiliation: Merck Research Laboratories, Palo Alto, CA 94304.
authors.forename: Barbara
authors.initials: B
authors.lastname: Joyce-Shaikh
authors.affiliation: Merck Research Laboratories, Palo Alto, CA 94304.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Cua
authors.affiliation: Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267; and michael.borchers@uc.edu.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Borchers
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D007249:Inflammation / Q000276:immunology; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology*; D008070:Lipopolysaccharides / Q000009:adverse effects; D008168:Lung / Q000473:pathology; D008262:Macrophage Activation / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology* / Q000473:pathology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology*; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
chemical_list: C509772:Clec5a protein, mouse; D016207:Cytokines; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D011956:Receptors, Cell Surface; D014028:Tobacco Smoke Pollution; D016178:Granulocyte-Macrophage Colony-Stimulating Factor