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Impaired Alveolar Macrophage Response to Haemophilus Antigens in Chronic Obstructive Lung Disease

Infectious Disease Division, Department of Veterans Affairs Western New York Healthcare System, State University of New York at Buffalo School of Medicine; and Laboratory of Flow Cytometry, Roswell Park Cancer Institute, Buffalo, New York

Correspondence and requests for reprints should be addressed to Charles S. Berenson, Division of Infectious Diseases (151), VA Western NY Healthcare System, 3495 Bailey Avenue, Buffalo, NY 14215. E-mail: berenson{at}acsu.buffalo.edu

Rationale: Interactions of nontypeable Haemophilus influenzae (NTHI) with macrophages are implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the immunologic mechanisms that mediate NTHI-macrophage inflammation are poorly understood. Outer membrane protein (OMP) P6 and lipooligosaccharide (LOS) of NTHI are potent immunomodulators. We theorized that alveolar macrophages in COPD possess fundamental immune defects that permit NTHI to evade host responses.

Objective: To test this hypothesis, we obtained human alveolar and blood macrophages from exsmokers with COPD, exsmokers without COPD, and nonsmokers.

Methods: Alveolar and blood macrophages from each donor were incubated with purified LOS and OMP P6 and with OMP P2 and the total outer membrane preparation (0.1–1 µg/ml).

Measurements: Supernatants (24 h) were assayed for IL-1, TNF-, IL-10, IL-12, and IL-8 by multianalyte multiplexed flow cytometry.

Results: Comparative induction of COPD and non-COPD alveolar macrophages by LOS and OMP P6 revealed diminished IL-8, TNF-, and IL-1 responses of COPD alveolar macrophages (p 0.03 for each). COPD alveolar macrophages also had diminished responses to total outer membrane (p 0.03 for each). In contrast, COPD blood macrophages had no significant differences among donor groups in IL-8, TNF-, or IL-1 responsiveness to NTHI antigens. Diminished IL-12 responses of COPD blood macrophages to NTHI antigens, compared with nonsmokers, could not be independently dissociated from group differences in age and pack-years.

Conclusions: These findings support a paradigm of defective immune responsiveness of alveolar macrophages, but not blood macrophages, in COPD.

Key Words: chronic obstructive pulmonary disease • macrophage, alveolar • nontypeable Haemophilus influenzae • phagocytosis

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