Impaired Phagocytosis of Nontypeable Haemophilus Influenzae by Human Alveolar Macrophages in Chronic Obstructive Pulmonary Disease

J Infect Dis. 2006 Nov 15;194(10):1375-84. doi: 10.1086/508428. Epub 2006 Oct 16.

Abstract

Background: Interactions of nontypeable Haemophilus influenzae (NTHI) with human alveolar macrophages are implicated in the persistence of NTHI in chronic obstructive pulmonary disease (COPD). However, the immunologic mechanisms that mediate NTHI-induced macrophage responses are poorly understood. We hypothesized that immunologic responses of alveolar macrophages to NTHI are impaired in COPD.

Methods: Blood and alveolar macrophages--obtained from ex-smokers with COPD (n = 14), ex-smokers without COPD (n = 15), and nonsmokers (n = 9)--were incubated with 3 distinct NTHI strains obtained from patients with COPD. Phagocytosis of 3H-NTHI, expressed as a percentage of the mean total radioactivity, and of intracellular viability, assessed as a percentage of viable cell-associated NTHI, were measured.

Results: Alveolar macrophages from donors with COPD, compared with those from donors without COPD, had impaired phagocytosis (median [interquartile range]) for each NTHI strain: 14P13H5, 0.26 (0.08-0.61) versus 1.36 (0.69-1.95); 6P5H1, 0.92 (0.32-1.82) versus 1.90 (1.32-2.68); and 14P14H1, 0.79 (0.23-1.32) versus 2.13 (1.13-2.40) (P < or = .01 for each). However, phagocytosis of all NTHI strains by blood macrophages from donors with COPD was indistinguishable from that of blood macrophages from donors without COPD and from nonsmokers. The intracellular killing of NTHI was not impaired in alveolar macrophages from donors with COPD.

Conclusions: These results support a paradigm of impaired phagocytosis by alveolar macrophages, but not blood macrophages, in COPD and provide an immunologic basis for persistence of NTHI in the airways of adults with COPD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Female
  • Haemophilus influenzae / immunology*
  • Humans
  • Macrophages / immunology
  • Macrophages / microbiology
  • Macrophages, Alveolar / immunology*
  • Macrophages, Alveolar / microbiology
  • Male
  • Microbial Viability
  • Middle Aged
  • Phagocytosis*
  • Pulmonary Disease, Chronic Obstructive / immunology*
  • Pulmonary Disease, Chronic Obstructive / microbiology*
  • Statistics as Topic