title: Beryllium increases the CD14(dim)CD16+ subset in the lung of chronic beryllium disease.
abstract: CD14dimCD16+ and CD14brightCD16+ cells, which compose a minor population of monocytes in human peripheral blood mononuclear cells (PBMC), have been implicated in several inflammatory diseases. The aim of this study was to investigate whether this phenotype was present as a subset of lung infiltrative alveolar macrophages (AMs) in the granulomatous lung disease, chronic beryllium disease (CBD). The monocytes subsets was determined from PBMC cells and bronchoalveolar lavage (BAL) cells from CBD, beryllium sensitized Non-smoker (BeS-NS) and healthy subjects (HS) using flow cytometry. The impact of smoking on the AMs cell phenotype was determined by using BAL cells from BeS smokers (BeS-S). In comparison with the other monocyte subpopulations, CD14dimCD16+ cells were at decreased frequency in PBMCs of both BeS-NS and CBD and showed higher HLA-DR expression, compared to HS. The AMs from CBD and BeS-NS demonstrated a CD14dimCD16+phenotype, while CD14brightCD16+ cells were found at increased frequency in AMs of BeS, compared to HS. Fresh AMs from BeS-NS and CBD demonstrated significantly greater CD16, CD40, CD86 and HLA-DR than HS and BeS-S. The expression of CD16 on AMs from both CBD and BeS-NS was downregulated significantly after 10μM BeSO4 stimulation. The phagocytic activity of AMs decreased after 10μM BeSO4 treatment in both BeS-NS and CBD, although was altered or reduced in HS and BeS-S. These results suggest that Be increases the CD14dimCD16+ subsets in the lung of CBD subjects. We speculate that Be-stimulates the compartmentalization of a more mature CD16+ macrophage phenotype and that in turn these macrophages are a source of Th1 cytokines and chemokines that perpetuate the Be immune response in CBD. The protective effect of cigarette smoking in BeS-S may be due to the low expression of co-stimulatory markers on AMs from smokers as well as the decreased phagocytic function.
authors.affiliation: Department of Medicine, National Jewish Health, Denver, Colorado, United States of America; Division of Pulmonary and Critical Care Sciences, Department of Medicine, School of Medicine, Denver, Colorado, United States of America.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Medicine, National Jewish Health, Denver, Colorado, United States of America; Division of Pulmonary and Critical Care Sciences, Department of Medicine, School of Medicine, Denver, Colorado, United States of America.
authors.forename: Nabeel
authors.initials: N
authors.lastname: Hamzeh
authors.affiliation: Department of Medicine, National Jewish Health, Denver, Colorado, United States of America.
authors.forename: May
authors.initials: M
authors.lastname: Gillespie
authors.affiliation: Department of Medicine, National Jewish Health, Denver, Colorado, United States of America.
authors.forename: Jill
authors.initials: J
authors.lastname: Elliott
authors.affiliation: Department of Pediatrics, Division of Pulmonary Medicine, Allergy and Immunology, Children's Hospital of Pittsburgh of University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Jieru
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Medicine, National Jewish Health, Denver, Colorado, United States of America; Division of Pulmonary and Critical Care Sciences, Department of Medicine, School of Medicine, Denver, Colorado, United States of America; Environmental Occupational Health Department, Colorado School of Public Health, University of Colorado, Denver, Colorado, United States of America.
authors.forename: Eva Brigitte
authors.initials: EB
authors.lastname: Gottschall
authors.affiliation: Department of Medicine, National Jewish Health, Denver, Colorado, United States of America.
authors.forename: Peggy M
authors.initials: PM
authors.lastname: Mroz
authors.affiliation: Department of Medicine, National Jewish Health, Denver, Colorado, United States of America; Division of Pulmonary and Critical Care Sciences, Department of Medicine, School of Medicine, Denver, Colorado, United States of America; Environmental Occupational Health Department, Colorado School of Public Health, University of Colorado, Denver, Colorado, United States of America.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Maier
mesh_terms: D000368:Aged; D001607:Berylliosis / Q000378:metabolism / Q000473:pathology*; D001608:Beryllium / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D018925:Chemokines / Q000378:metabolism; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008168:Lung / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects; D010641:Phenotype; D017452:Receptors, IgG / Q000378:metabolism*
chemical_list: D018925:Chemokines; D016207:Cytokines; D006684:HLA-DR Antigens; D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG; C020711:beryllium sulfate; D001608:Beryllium