Hyperoxia-induced emphysematous changes in subacute phase of endotoxin-induced lung injury in rats.
We examined the effects of prolonged hyperoxia (75% O(2)) on lung structure and collagen metabolism in the subacute phase of lung injury induced by continuous infusion of endotoxin (LPS) in a rat model. Experimental groups included control, endotoxin alone, endotoxin plus hyperoxia, and hyperoxia alone. Endotoxin-treated rats received a bolus of LPS (10 mg/kg i.v.) followed by 500 microg.kg(-1).day(-1) in continuous infusion for 10 days. The bronchoalveolar lavage (BAL) fluid/plasma albumin concentration ratio, an index of capillary permeability, and neutrophil and macrophage counts in BAL fluid were highest in the endotoxin plus hyperoxia group. On pathological examination, prolonged hyperoxia exacerbated destruction of the alveolar wall and caused most prominent emphysematous changes in the endotoxin plus hyperoxia group. Lung tissue hydroxyproline concentration was significantly decreased in the hyperoxia group and increased in the endotoxin group. The latent forms of MMP-2 and MMP-9 increased in BAL fluid of the endotoxin- and/or hyperoxia-treated groups, whereas the activities of collagenase and gelatinase, and the active form of MMP-2 were all increased in the hyperoxia-treated groups. Added to endotoxin, prolonged hyperoxia degraded collagen, the major structural component of basement membranes, and caused emphysematous changes associated with activation of collagenase and MMP-2. Our observations suggest that, in the subacute phase of endotoxin-induced lung injury, prolonged hyperoxia causes pulmonary emphysematous changes with persistent injury to the alveolar capillary barrier. Collagenase and MMP-2 activated by hyperoxia, together with MMP-9, may play prominent roles in disruption of the alveolar basement membranes and degradation of collagen lining the alveolar walls.
Department of Surgery, Tokyo Metropolitan Komagome Hospital, Japan.
Mitsutomo
M
Kohno
Akitoshi
A
Ishizaka
Makoto
M
Sawafuji
Hidefumi
H
Koh
Yoshitaka
Y
Hirayama
Eiji
E
Ikeda
Takayuki
T
Shiomi
Akira
A
Ohashi
Yasunori
Y
Okada
Koichi
K
Kobayashi
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D002452:Cell Count; D003094:Collagen / Q000378:metabolism; D017364:Collagenases / Q000378:metabolism; D004646:Emphysema / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D004731:Endotoxins; D018093:Gelatinases / Q000378:metabolism; D018496:Hyperoxia / Q000150:complications*; D008171:Lung Diseases / Q000139:chemically induced* / Q000150:complications / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000378:metabolism / Q000473:pathology; D011654:Pulmonary Edema / Q000139:chemically induced / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000378:metabolism
D004731:Endotoxins; D012709:Serum Albumin; D003094:Collagen; D017364:Collagenases; D018093:Gelatinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9