Cigarette smoke decreases MARCO expression in macrophages: implication in Mycoplasma pneumoniae infection.
Bacterial infections including Mycoplasma pneumoniae (Mp) are a major cause of exacerbations in chronic obstructive pulmonary disease (COPD). Cigarette smoke (CS) is the leading cause of COPD, and affects the function of alveolar macrophages that act as the first line of defense against the invading respiratory pathogens. Macrophages express a transmembrane receptor called macrophage receptor with collagenous structure (MARCO) that is involved in the clearance of microorganisms. Whether CS down-regulates MARCO and eventually decreases the clearance of Mp has not been investigated. We utilized human monocytic cell line (THP-1)-derived macrophages to examine the effects of CS extract (CSE) on MARCO expression and Mp growth. Specifically, macrophages were pre-exposed to CSE for 6 h, and then infected with or without Mp for 2 h. MARCO was examined at both mRNA and protein levels by using real-time PCR and immunofluorescent staining, respectively. Mp in the supernatants was quantified by quantitative culture. In addition, a neutralizing MARCO antibody was added to macrophages to test if blockade of MARCO impaired Mp clearance. We found that CSE significantly decreased MARCO expression in a dose-dependant manner at 6 h post-CSE. Mp levels in CSE-treated cells were higher than those in non-CSE-treated cells, indicating a decreased pathogen clearance. Additionally, neutralizing MARCO in macrophages markedly increased Mp levels. Our results indicate that cigarette smoke exposure down-regulates MARCO expression in macrophages, which may be in part responsible for impaired bacterial (e.g., Mp) clearance.
Baqir
Misbah
M
Department of Medicine, National Jewish Medical and Research Center, University of Colorado Health Sciences Center, Denver, CO 80206, USA.
Chen
Chiung-Zuei
CZ
Martin
Richard J
RJ
Thaikoottathil
Jyoti
J
Case
Stephanie R
SR
Minor
Maisha N
MN
Bowler
Russell
R
Chu
Hong Wei
HW
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D009177:Mycoplasma pneumoniae / Q000276:immunology / Q000378:metabolism*; D016133:Polymerase Chain Reaction / Q000379:methods; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000378:metabolism*; D012906:Smoke / Q000009:adverse effects; D014026:Nicotiana / Q000009:adverse effects
C092228:Marco protein, mouse; D011971:Receptors, Immunologic; D012906:Smoke