Impaired alveolar macrophage response to Haemophilus antigens in chronic obstructive lung disease.
BACKGROUND
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 microg/ml).


METHODS
Supernatants (24 h) were assayed for IL-1beta, TNF-alpha, 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-alpha, and IL-1beta responses of COPD alveolar macrophages (p < or = 0.03 for each). COPD alveolar macrophages also had diminished responses to total outer membrane (p < or = 0.03 for each). In contrast, COPD blood macrophages had no significant differences among donor groups in IL-8, TNF-alpha, or IL-1beta 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.
Infectious Disease Division, Department of Veterans Affairs Western New York Healthcare System, State University of New York at Buffalo School of Medicine, Buffalo, NY 14215, USA. berenson@acsu.buffalo.edu
Charles S
CS
Berenson
Catherine T
CT
Wrona
Lori J
LJ
Grove
Jane
J
Maloney
Mary Alice
MA
Garlipp
Paul K
PK
Wallace
Carleton C
CC
Stewart
Sanjay
S
Sethi
D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000276:immunology*; D016022:Case-Control Studies; D018929:Cell Culture Techniques; D005260:Female; D006193:Haemophilus influenzae / Q000276:immunology*; D006801:Humans; D007378:Interleukins / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D012907:Smoking / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000942:Antigens, Bacterial; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha