Increased expression of gelatinases and collagenase in rat lungs exposed to 100% oxygen.
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.
Facultad de Ciencias, UNAM, Coyoacán, Mexico.
A
A
Pardo
M
M
Selman
K
K
Ridge
R
R
Barrios
J I
JI
Sznajder
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D017364:Collagenases / Q000378:metabolism*; D018093:Gelatinases / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008168:Lung / Q000201:enzymology*; D016676:Macrophages, Alveolar / Q000201:enzymology; D008297:Male; D020781:Matrix Metalloproteinase 1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000378:metabolism*; D010100:Oxygen / Q000009:adverse effects*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000201:enzymology* / Q000209:etiology; D013047:Specific Pathogen-Free Organisms; D015854:Up-Regulation
D012333:RNA, Messenger; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1; D010100:Oxygen