title: Paradoxically decreased intracellular collagenase activity in macrophages from bronchoalveolar lavage fluid in current smokers and patients with obstructive ventilatory disorder.
abstract: The roles of matrix metalloproteinases (MMPs) in chronic obstructive pulmonary disease (COPD) have been studied. Macrophages are considered to release MMPs in the lung tissue. We measured intracellular collagenase activity in intact CD14(+)CD45++ cells from the bronchoalveolar lavage fluid (BALF) of patients with obstructive ventilatory impairment and other respiratory diseases. Collagenase activity in current smokers was significantly lower than those in non-smokers (3.25+/-0.54 versus 5.48+/-0.55; P=0.006), and also lower than those in ex-smokers (versus 6.54+/-1.54; P=0.019). We found a lower activity of collagenase in patients with FEV1/FVC below 70% than those with 70% or higher (2.68+/-0.59 versus 4.51+/-0.44; P=0.034). Mean value of FEV1/FVC in patients with collagenase activity of 4 or higher was significantly elevated as compared to those with the activity lower than 4 (83.3+/-3.3 versus 71.8+/-4.9; P=0.021). The discrepancy between increased release of MMPs by previous reports and decreased intracellular activity in our results, may be explained by the production of inactive form of MMPs is relatively increased in COPD. Our study may provide the future direction in investigating the mechanism of COPD. In clinics, this measurement in patients with smoking habits may be helpful to advise them to stop smoking, and to avoid progression to the irreversible obstructive disease.
authors.affiliation: First Department of Internal Medicine, Tokyo Medical University, Tokyo 160-0023, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Hakoda
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Ito
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Ohkubo
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Tago
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Yoshida
authors.forename: Kazushige
authors.initials: K
authors.lastname: Minemura
authors.forename: Kenta
authors.initials: K
authors.lastname: Utsumi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Aoshima
authors.forename: Kazuma
authors.initials: K
authors.lastname: Ohyashiki
mesh_terms: D000328:Adult; D000368:Aged; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D017364:Collagenases / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D017493:Leukocyte Common Antigens / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D016676:Macrophages, Alveolar / Q000201:enzymology*; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000201:enzymology*; D012907:Smoking / Q000009:adverse effects*
chemical_list: D018950:Lipopolysaccharide Receptors; D017493:Leukocyte Common Antigens; D017364:Collagenases