Smoking alters alveolar macrophage recognition and phagocytic ability: implications in chronic obstructive pulmonary disease.
Chronic obstructive pulmonary disease (COPD) is associated with defective efferocytosis (apoptosis and alveolar macrophage [AM] phagocytic function) that may lead to secondary necrosis and tissue damage. We investigated ex vivo AM phagocytic ability and recognition molecules (CD36, integrin alphaVbeta3, CD31, CD91, CD44) using flow cytometry. The transferrin receptor (CD71) was measured as an indicator of monocyte-macrophage differentiation in bronchoalveolar lavage (BAL). Proliferation was assessed with Ki-67. Based on evidence of systemic involvement in COPD, blood from 17 current smokers and 25 ex-smokers with COPD, 22 healthy smokers, and 20 never-smoking control subjects was also investigated. BAL was collected from 10 to 16 subjects in each group. Levels of recognition molecules and cAMP were assessed after exposure of AM to cigarette smoke in vitro. The phagocytic ability of AM was significantly decreased in both COPD groups and in healthy smokers compared with control subjects. However, phagocytic capacity was better in subjects with COPD who had ceased smoking, compared with those who were still smoking. AM from current smokers with COPD and healthy smokers exhibited reduced CD31, CD91, CD44, and CD71, and enhanced Ki-67 compared with healthy never-smoker control subjects. There were no differences in these markers in AM from ex-smokers with COPD compared with control subjects, or in blood monocytes from any group. Suppressive effects of cigarette smoke on AM recognition molecules associated with an increase in cAMP were confirmed in vitro. Our data indicates that a smoking-related reduction in AM phagocytic ability and expression of several important recognition molecules may be at least partially normalized in those subjects with COPD who have ceased smoking.
Hodge
Sandra
S
Department of Thoracic Medicine, Royal Adelaide Hospital and Lung Research Laboratory, Hanson Institute, Adelaide, South Australia. sandy.hodge@imvs.sa.gov.au
Hodge
Greg
G
Ahern
Jessica
J
Jersmann
Hubertus
H
Holmes
Mark
M
Reynolds
Paul N
PN
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects; D001772:Blood Cell Count; D001980:Bronchi / Q000166:cytology / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D003710:Demography; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000473:pathology*; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects; D010587:Phagocytosis / Q000187:drug effects*; D029424:Pulmonary Disease, Chronic Obstructive / Q000473:pathology*; D012907:Smoking / Q000009:adverse effects*
D008565:Membrane Proteins; D000242:Cyclic AMP