Increased expression of gelatinases and collagenase in rat lungs exposed to 100% oxygen

Am J Respir Crit Care Med. 1996 Oct;154(4 Pt 1):1067-75. doi: 10.1164/ajrccm.154.4.8887609.


Exposure of adult rats to 100% O2 produces a lethal injury by 72 h. We reasoned that matrix metalloproteinases participate in the pathogenesis of hyperoxic lung injury. To that end we studied the expression and activity of gelatinases A and B and interstitial collagenase in lung tissues and bronchoalveolar lavage fluids (BALF) of rats exposed to 100% oxygen for 60 h. Gelatin zymography of BALF samples revealed a 472 kDa molecular species both in controls and oxygen-exposed animals. In addition, BALF from hyperoxic rats exhibited a 95-kDa gelatinase. Likewise, BALF total gelatinolytic and collagenolytic activities were significantly increased in oxygen-exposed rats. In situ hybridization revealed an increase in type IV collagenases as well as interstitial collagenase mRNAs in the oxygen-exposed lungs. The three enzymes were expressed by alveolar macrophages, and in variable degrees by interstitial and alveolar epithelial cells. Immunoreactive gelatinase B and collagenase paralleled the cell localization of the mRNAs but were also detected in the alveolar walls and interstitium. In situ zymography showed gelatinolytic activity in frozen sections of oxygen-exposed lungs but not in normal lungs. The upregulation of these metalloproteinases during acute exposure to 100% O2 suggests that they might contribute to hyperoxic lung damage through the degradation of extracellular matrix components.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid / chemistry
  • Collagenases / metabolism*
  • Gelatinases / metabolism*
  • Immunohistochemistry
  • In Situ Hybridization
  • Lung / enzymology*
  • Macrophages, Alveolar / enzymology
  • Male
  • Matrix Metalloproteinase 1
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Metalloendopeptidases / metabolism*
  • Oxygen / adverse effects*
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Respiratory Distress Syndrome / enzymology*
  • Respiratory Distress Syndrome / etiology
  • Specific Pathogen-Free Organisms
  • Up-Regulation


  • RNA, Messenger
  • Collagenases
  • Gelatinases
  • Metalloendopeptidases
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Matrix Metalloproteinase 1
  • Oxygen