title: Pivotal Advance: Expansion of small sputum macrophages in CF: failure to express MARCO and mannose receptors.
abstract: Macrophages in the airways form an important element of immune defense and inflammation. We analyzed induced sputum from airways of patients with CF for the types of macrophages present, their receptor expression, and phagocytic function. In samples from patients and age-matched controls, macrophages were analyzed by multicolor flow cytometry, scavenger receptor expression was studied at the protein and mRNA level, and receptor function was investigated using fluorescent particles. In adult patients with CF, we discovered a pronounced expansion of the small CD14+ DR+ CD68weak+ macrophages to 73 +/- 18% compared with 16 +/- 8% in healthy controls. Expression of the MARCO and CD206 (mannose receptor) was strongly reduced at the mRNA and protein level in sputum macrophages. Antibody-blocking studies showed that MARCO mediates phagocytosis of unopsonized particles. In line with reduced MARCO expression, sputum macrophages in CF showed a deficient uptake of particles (23+/-9% of cells) compared with healthy controls (71+/-15%). The deficiency of MARCO expression in the predominant small sputum macrophages in CF may lead to impaired clearance of inhaled particles with increased inflammation and damage to the CF lung.
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom.
authors.forename: Adam K A
authors.initials: AK
authors.lastname: Wright
authors.forename: Satish
authors.initials: S
authors.lastname: Rao
authors.forename: Simon
authors.initials: S
authors.lastname: Range
authors.forename: Christiane
authors.initials: C
authors.lastname: Eder
authors.forename: Thomas P J
authors.initials: TP
authors.lastname: Hofer
authors.forename: Marion
authors.initials: M
authors.lastname: Frankenberger
authors.forename: Lester
authors.initials: L
authors.lastname: Kobzik
authors.forename: Chris
authors.initials: C
authors.lastname: Brightling
authors.forename: Jonathan
authors.initials: J
authors.lastname: Grigg
authors.forename: Loems
authors.initials: L
authors.lastname: Ziegler-Heitbrock
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D016022:Case-Control Studies; D003550:Cystic Fibrosis / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism*; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism*; D008875:Middle Aged; D052638:Particulate Matter / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D051116:Receptors, Scavenger / Q000378:metabolism; D013183:Sputum / Q000166:cytology*; D013194:Staining and Labeling; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D006684:HLA-DR Antigens; D037181:Lectins, C-Type; D018950:Lipopolysaccharide Receptors; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D052638:Particulate Matter; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C490460:MARCO protein, human