Published ahead of print on April 24, 2003, doi:10.1164/rccm.200301-103OC
American Journal of Respiratory and Critical Care Medicine Vol 168. pp. 222-227, (2003)
© 2003 American Thoracic Society
Extracellular Matrix Metalloproteinase Inducer Is Increased in Smokers' Bronchoalveolar Lavage Fluid
Tomoko Betsuyaku,
Mishie Tanino,
Katsura Nagai,
Yasuyuki Nasuhara,
Masaharu Nishimura and
Robert M. Senior
First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan, and the Departments of Medicine and Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri
Correspondence and requests for reprints should be addressed to Tomoku Betsuyaku, M.D., Ph.D., First Department of Medicine, Hokkaido University School of Medicine, N-15, W-7, Kita-ku, Sapporo 060-8638, Japan. E-mail: bytomoko{at}med.hokudai.ac.jp
Extracellular matrix metalloproteinase inducer (EMMPRIN), also called basigin, is present in the lung during development, but its expression in normal adult lung is minimal. Increases of EMMPRIN have been found in various forms of experimental lung injury. To determine whether EMMPRIN might be involved in alveolar injury/repair associated with smoking, we developed an ELISA for EMMPRIN and applied it to bronchoalveolar lavage fluids from never-smokers (n = 7), former smokers (n = 16), and current smokers (n = 58). The smoker groups included subjects with emphysema, as determined by high-resolution chest computed tomography. EMMPRIN levels were significantly elevated in current and former smokers (315 ± 20 and 175 ± 15 pg/ml SEM, respectively, compared with 31 ± 7 pg/ml in never-smokers), but the EMMPRIN levels of smokers with emphysema were not different from smokers without emphysema. Immunohistochemistry of smokers' lung tissue showed EMMPRIN in bronchiolar epithelium and alveolar macrophages, but EMMPRIN mRNA in alveolar macrophages was not different between current and never-smokers. Matrix metalloproteinase-1 was also detectable in the bronchoalveolar lavage fluid from some smokers but not in never-smokers. These findings indicate that smoking is associated with increased intrapulmonary EMMPRIN. Whether EMMPRIN is involved in smoking-induced lung pathology remains to be determined.
Key Words: smoking • emphysema • matrix metalloproteinases • alveolar macrophages
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