Airway obstruction correlates with collagenase-2 (MMP-8) expression and activation in bronchial asthma

Lab Invest. 2002 Nov;82(11):1535-45. doi: 10.1097/01.lab.0000035023.53893.b6.

Abstract

Matrix metalloproteinases (MMPs) contribute to extracellular matrix and basement membrane degradation in asthma. The present study analyzed molecular forms and degree of activation and expression of MMP-8 in bronchoalveolar lavage fluid (BALF), BALF cells, and bronchial tissue specimens from 14 steroid-naive asthma patients, 13 uncontrolled severe asthma patients, 13 controlled asthma patients, and 14 healthy subjects by Western immunoblotting, immunohistochemistry, and in situ hybridization. Immunohistochemistry and in situ hybridization revealed a prominent MMP-8 immunoreactivity in submucosal inflammatory, glandular, and shed, but not in intact bronchial epithelial cells of asthma patients. In BALF cytospins, both MMP-8 protein and mRNA expression were observed in epithelial cells, macrophages, and polymorphonuclear leukocytes (PMNs). MMP-8 was present in BALFs asthma patients in complex, pro- and active PMN-type, and pro- and active non-PMN-type forms. BALF MMP-8 was significantly converted to active form only in BALFs from steroid-naive and uncontrolled severe asthma patients, but not in BALFs from well-controlled asthma patients or healthy controls. A significant inverse correlation between BALF MMP-8 levels and FEV1 (r = -0.283, p = 0.04), and BALF activated MMP-8 forms and FEV1 (r = -0.427, p = 0.001) was detected. Overall, these data suggest that MMP-8 and its activation has an important role in the airway destruction, healing, remodeling, and treatment response in asthma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Airway Obstruction / enzymology*
  • Asthma / enzymology*
  • Asthma / physiopathology
  • Blotting, Western
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / cytology
  • Enzyme Activation
  • Female
  • Forced Expiratory Volume
  • Humans
  • Immunohistochemistry
  • Male
  • Matrix Metalloproteinase 8 / analysis*
  • Matrix Metalloproteinase 8 / genetics
  • Middle Aged
  • RNA, Messenger / analysis

Substances

  • RNA, Messenger
  • Matrix Metalloproteinase 8