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

• Published in: The Journal of infectious diseases 2006-11, Vol.194 (10), p.1375-1384
• Main Authors: Berenson, Charles S., Garlipp, Mary Alice, Grove, Lori J., Maloney, Jane, Sethi, Sanjay
• Format: Article
• Language: English
• Subjects: Aged; Alveolar macrophages; Bacteria; Bacterial diseases; Bacterial diseases of the respiratory system; Bacteriology; Bacteriophages; Biological and medical sciences; Blood; Chronic obstructive pulmonary disease; Female; Fundamental and applied biological sciences. Psychology; Haemophilus influenzae; Haemophilus influenzae - immunology; Human bacterial diseases; Humans; Infectious diseases; Lung diseases; Macrophages; Macrophages - immunology; Macrophages - microbiology; Macrophages, Alveolar - immunology; Macrophages, Alveolar - microbiology; Male; Medical sciences; Microbial Viability; Microbiology; Middle Aged; Miscellaneous; Phagocytosis; Pulmonary alveoli; Pulmonary Disease, Chronic Obstructive - immunology; Pulmonary Disease, Chronic Obstructive - microbiology; Statistics as Topic
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/508428

BackgroundInteractions 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 MethodsBlood 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 ResultsAlveolar 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⩽.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 ConclusionsThese 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