title: Phagocytic dysfunction of human alveolar macrophages and severity of chronic obstructive pulmonary disease.
abstract: BACKGROUND
  Alveolar macrophages in chronic obstructive pulmonary disease (COPD) have fundamental impairment of phagocytosis for nontypeable Haemophilus influenzae (NTHI). However, relative selectivity of dysfunctional phagocytosis among diverse respiratory pathogens: NTHI, Moraxella catarrhalis (MC), Streptococcus pneumoniae (SP), and nonbacterial particles, as well as the contribution of impaired phagocytosis to severity of COPD, has not been explored.
  
  
  METHODS
  Alveolar macrophages, obtained from nonsmokers (n = 20), COPD ex-smokers (n = 32), and COPD active smokers (n = 64), were incubated with labeled NTHI, MC, SP, and fluorescent microspheres. Phagocytosis was measured as intracellular percentages of each.
  
  
  RESULTS
  Alveolar macrophages of COPD ex-smokers and active smokers had impaired complement-independent phagocytosis of NTHI (P = .003) and MC (P = .0007) but not SP or microspheres. Nonetheless, complement-mediated phagocytosis was enhanced within each group only for SP. Defective phagocytosis was significantly greater for NTHI than for MC among COPD active smokers (P < .0001) and ex-smokers (P = .028). Moreover, severity of COPD (FEV1%predicted) correlated with impaired AM phagocytosis for NTHI (P = .0016) and MC (P = .01).
  
  
  CONCLUSIONS
  These studies delineate pathogen- and host-specific differences in defective alveolar macrophages phagocytosis of respiratory bacteria in COPD, further elucidating the immunologic basis for bacterial persistence in COPD and provide the first demonstration of association of impaired phagocytosis to severity of disease.
authors.affiliation: Infectious Disease and Pulmonary Medicine Divisions, Department of Veterans Affairs Western New York Healthcare System, State University of New York at Buffalo School of Medicine.
authors.forename: Charles S
authors.initials: CS
authors.lastname: Berenson
authors.forename: Ragina L
authors.initials: RL
authors.lastname: Kruzel
authors.forename: Ellana
authors.initials: E
authors.lastname: Eberhardt
authors.forename: Sanjay
authors.initials: S
authors.lastname: Sethi
mesh_terms: D000368:Aged; D002478:Cells, Cultured; D005260:Female; D006193:Haemophilus influenzae / Q000302:isolation & purification; D006801:Humans; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000502:physiology*; D008297:Male; D008863:Microspheres; D008875:Middle Aged; D001936:Moraxella catarrhalis / Q000302:isolation & purification; D010587:Phagocytosis / Q000276:immunology / Q000502:physiology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism / Q000382:microbiology / Q000503:physiopathology*; D012044:Regression Analysis; D012907:Smoking; D013296:Streptococcus pneumoniae / Q000302:isolation & purification
keywords: COPD; Moraxella catarrhalis; Streptococcus pneumoniae; alveolar macrophage; nontypeable Haemophilus influenzae; phagocytosis
references.citation: J Exp Med. 2004 Jul 19;200(2):267-72
references.pmid: 15263032
references.citation: Clin Microbiol Rev. 2001 Apr;14(2):336-63
references.pmid: 11292642
references.citation: Annu Rev Immunol. 2002;20:825-52
references.pmid: 11861619
references.citation: Eur J Clin Microbiol Infect Dis. 2009 Aug;28(8):971-6
references.pmid: 19360444
references.citation: Am J Respir Crit Care Med. 2008 Mar 1;177(5):491-7
references.pmid: 18079493
references.citation: Am J Respir Crit Care Med. 2006 Jul 1;174(1):31-40
references.pmid: 16574934
references.citation: Infect Immun. 2000 Apr;68(4):2286-93
references.pmid: 10722631
references.citation: Am J Respir Crit Care Med. 2008 Apr 15;177(8):861-70
references.pmid: 18174544
references.citation: Am J Respir Crit Care Med. 2004 Aug 1;170(3):266-72
references.pmid: 15117742
references.citation: Infect Immun. 2008 Apr;76(4):1599-607
references.pmid: 18227159
references.citation: J Infect Dis. 2006 Nov 15;194(10):1375-84
references.pmid: 17054066
references.citation: Am J Respir Crit Care Med. 2000 Sep;162(3 Pt 1):947-52
references.pmid: 10988111
references.citation: Infect Immun. 2005 Jun;73(6):3471-8
references.pmid: 15908376
references.citation: J Infect Dis. 2007 Sep 15;196(6):928-35
references.pmid: 17703425
references.citation: Infect Immun. 1994 Feb;62(2):673-9
references.pmid: 7507900
references.citation: Am J Respir Crit Care Med. 2005 Jul 15;172(2):195-9
references.pmid: 15805178
references.citation: Am J Med. 2000 Sep;109(4):288-95
references.pmid: 10996579
references.citation: Am J Respir Crit Care Med. 2004 Feb 15;169(4):448-53
references.pmid: 14597486
references.citation: Am J Respir Crit Care Med. 2008 Jul 15;178(2):139-48
references.pmid: 18420960
references.citation: Am J Respir Crit Care Med. 2002 Apr 1;165(7):967-71
references.pmid: 11934723
references.citation: Am J Respir Crit Care Med. 2007 Sep 15;176(6):532-55
references.pmid: 17507545
references.citation: J Biol Chem. 2004 May 14;279(20):21421-30
references.pmid: 14993215
references.citation: Infect Immun. 2009 Oct;77(10):4232-42
references.pmid: 19620348
references.citation: N Engl J Med. 2004 Jun 24;350(26):2645-53
references.pmid: 15215480
references.citation: Am Rev Respir Dis. 1980 Jan;121(1):65-71
references.pmid: 7352714
references.citation: Science. 2004 May 14;304(5673):1014-8
references.pmid: 15143282
references.citation: N Engl J Med. 2005 May 12;352(19):1967-76
references.pmid: 15888697
references.citation: N Engl J Med. 2002 Aug 15;347(7):465-71
references.pmid: 12181400
references.citation: Infect Immun. 2010 Jul;78(7):3129-35
references.pmid: 20439480
references.citation: Thorax. 2002 Sep;57(9):759-64
references.pmid: 12200518
references.citation: Am J Respir Crit Care Med. 2003 Apr 15;167(8):1090-5
references.pmid: 12684248
references.citation: Infect Immun. 2005 Dec;73(12):8161-6
references.pmid: 16299311
references.citation: FEMS Microbiol Lett. 2001 Sep 11;203(1):55-61
references.pmid: 11557140
references.citation: Immunol Cell Biol. 2003 Aug;81(4):289-96
references.pmid: 12848850
references.citation: Infect Immun. 2010 Mar;78(3):1214-20
references.pmid: 20008540
references.citation: Int J Tissue React. 1996;18(4-6):109-14
references.pmid: 9195246
references.citation: Eur Respir J. 2010 May;35(5):1039-47
references.pmid: 19897561
references.citation: Sci Transl Med. 2011 Apr 13;3(78):78ra32
references.pmid: 21490276
references.citation: J Biol Chem. 2009 Mar 20;284(12):7495-504
references.pmid: 19155216