title: Attenuation of host defense function of lung phagocytes in young cystic fibrosis patients.
abstract: BACKGROUND
  Recent reports suggest that endotoxin exposure can blunt phagocyte functions. The aim of this study was to examine whether lung phagocytic cells have altered host defense function in young cystic fibrosis (CF) patients, and to explore the contribution of neutrophil elastase (NE) and surfactant proteins to these effects.
  
  
  METHODS
  BALF cells from CF children (N=12) and disease controls (N=12) were analyzed by flow cytometry for mCD14 and HLA-DR expression and phagocytosis. The effects of exogenous surfactant protein A and D (SP-A,D) and proteases on BALF cells in short term culture were assessed experimentally.
  
  
  RESULTS
  Expression of the surface markers mCD14 and HLA-DR, and phagocytosis, were all blunted on CF phagocytes compared to disease controls (p<0.05). In CF phagocytes, SP-A enhanced both phagocytosis and mCD14 expression (p<0.05). Both CF BALF and NE reduced phagocytosis and expression of mCD14 and HLA-DR (p<0.05) by non-CF phagocytes; the latter effect was attenuated by protease inhibitor.
  
  
  CONCLUSIONS
  CF airway phagocytes appear to have altered host defense functions that could contribute to poor bacterial clearance. These impairments can be reproduced by incubation of non-CF cells with NE, while SP-A can partially reverse them. Decreasing protease activity and increasing collectin activity may be beneficial in early CF.
authors.affiliation: Center for Environmental Medicine, Asthma and Lung Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Neil E
authors.initials: NE
authors.lastname: Alexis
authors.forename: Marianne S
authors.initials: MS
authors.lastname: Muhlebach
authors.forename: David B
authors.initials: DB
authors.lastname: Peden
authors.forename: Terry L
authors.initials: TL
authors.lastname: Noah
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D001999:Bronchoscopy; D002478:Cells, Cultured; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000096:biosynthesis*; D006801:Humans; D066298:In Vitro Techniques; D019272:Leukocyte Elastase / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis*; D008297:Male; D010586:Phagocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology*; D037662:Pulmonary Surfactant-Associated Protein A / Q000494:pharmacology; D037663:Pulmonary Surfactant-Associated Protein D / Q000494:pharmacology; D011663:Pulmonary Surfactants / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D006684:HLA-DR Antigens; D018950:Lipopolysaccharide Receptors; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D011663:Pulmonary Surfactants; D019272:Leukocyte Elastase