title: A CCL24-dependent pathway augments eosinophilic airway inflammation in house dust mite-challenged Cd163(-/-) mice.
abstract: CD163 is a macrophage scavenger receptor with anti-inflammatory and pro-inflammatory functions. Here, we report that alveolar macrophages (AMΦs) from asthmatic subjects had reduced cell-surface expression of CD163, which suggested that CD163 might modulate the pathogenesis of asthma. Consistent with this, house dust mite (HDM)-challenged Cd163(-/-) mice displayed increases in airway eosinophils and mucous cell metaplasia (MCM). The increased airway eosinophils and MCM in HDM-challenged Cd163(-/-) mice were mediated by augmented CCL24 production and could be reversed by administration of a neutralizing anti-CCL24 antibody. A proteomic analysis identified the calcium-dependent binding of CD163 to Dermatophagoides pteronyssinus peptidase 1 (Der p1). Der p1-challenged Cd163(-/-) mice had the same phenotype as HDM-challenged Cd163(-/-) mice with increases in airway eosinophils, MCM and CCL24 production, while Der p1 induced CCL24 secretion by bone marrow-derived macrophages (BMMΦs) from Cd163(-/-) mice, but not BMMΦs from wild-type (WT) mice. Finally, airway eosinophils and bronchoalveolar lavage fluid CCL24 levels were increased in Der p1-challenged WT mice that received adoptively transferred AMΦ's from Cd163(-/-) mice. Thus, we have identified CD163 as a macrophage receptor that binds Der p1. Furthermore, we have shown that HDM-challenged Cd163(-/-) mice have increased eosinophilic airway inflammation and MCM that are mediated by a CCL24-dependent mechanism.
authors.affiliation: Laboratory of Asthma and Lung Inflammation, NHLBI, NIH, Bethesda, Maryland, USA.
authors.forename: C
authors.initials: C
authors.lastname: Dai
authors.affiliation: Laboratory of Asthma and Lung Inflammation, NHLBI, NIH, Bethesda, Maryland, USA.
authors.forename: X
authors.initials: X
authors.lastname: Yao
authors.affiliation: Laboratory of Asthma and Lung Inflammation, NHLBI, NIH, Bethesda, Maryland, USA.
authors.forename: E M
authors.initials: EM
authors.lastname: Gordon
authors.affiliation: Laboratory of Asthma and Lung Inflammation, NHLBI, NIH, Bethesda, Maryland, USA.
authors.forename: A
authors.initials: A
authors.lastname: Barochia
authors.affiliation: Laboratory of Asthma and Lung Inflammation, NHLBI, NIH, Bethesda, Maryland, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Cuento
authors.affiliation: Laboratory of Asthma and Lung Inflammation, NHLBI, NIH, Bethesda, Maryland, USA.
authors.forename: M
authors.initials: M
authors.lastname: Kaler
authors.affiliation: Laboratory of Asthma and Lung Inflammation, NHLBI, NIH, Bethesda, Maryland, USA.
authors.forename: K S
authors.initials: KS
authors.lastname: Meyer
authors.affiliation: Animal Surgery and Resources Core Facility, NHLBI, NIH, Bethesda, Maryland, USA.
authors.forename: K J
authors.initials: KJ
authors.lastname: Keeran
authors.affiliation: Animal Surgery and Resources Core Facility, NHLBI, NIH, Bethesda, Maryland, USA.
authors.forename: G Z
authors.initials: GZ
authors.lastname: Nugent
authors.affiliation: Animal Surgery and Resources Core Facility, NHLBI, NIH, Bethesda, Maryland, USA.
authors.forename: K R
authors.initials: KR
authors.lastname: Jeffries
authors.affiliation: Pathology Core Facility, NHLBI, NIH, Bethesda, Maryland, USA.
authors.forename: X
authors.initials: X
authors.lastname: Qu
authors.affiliation: Pathology Core Facility, NHLBI, NIH, Bethesda, Maryland, USA.
authors.forename: Z-X
authors.initials: ZX
authors.lastname: Yu
authors.affiliation: Proteomics Core Facility, NHLBI, NIH, Bethesda, Maryland, USA.
authors.forename: A
authors.initials: A
authors.lastname: Aponte
authors.affiliation: Proteomics Core Facility, NHLBI, NIH, Bethesda, Maryland, USA.
authors.forename: M
authors.initials: M
authors.lastname: Gucek
authors.affiliation: Flow Cytometry Core Facility, NHLBI, NIH, Bethesda, Maryland, USA.
authors.forename: P K
authors.initials: PK
authors.lastname: Dagur
authors.affiliation: Flow Cytometry Core Facility, NHLBI, NIH, Bethesda, Maryland, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: McCoy
authors.affiliation: Laboratory of Asthma and Lung Inflammation, NHLBI, NIH, Bethesda, Maryland, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Levine
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000008:administration & dosage; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D039741:Antigens, Dermatophagoides / Q000276:immunology / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000378:metabolism*; D060829:Arthropod Proteins / Q000276:immunology / Q000378:metabolism; D001249:Asthma / Q000276:immunology*; D002465:Cell Movement; D002478:Cells, Cultured; D054423:Chemokine CCL24 / Q000276:immunology / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000276:immunology / Q000378:metabolism; D004804:Eosinophils / Q000276:immunology*; D006801:Humans; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000637:transplantation; D008679:Metaplasia; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D039981:Pyroglyphidae; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000473:pathology*; D000098902:CD163 Antigen
chemical_list: D057134:Antibodies, Neutralizing; D015703:Antigens, CD; D039741:Antigens, Dermatophagoides; D015214:Antigens, Differentiation, Myelomonocytic; D060829:Arthropod Proteins; D000098902:CD163 Antigen; D054423:Chemokine CCL24; D011956:Receptors, Cell Surface; D003546:Cysteine Endopeptidases; C451162:Dermatophagoides pteronyssinus antigen p 1