TY - JOUR
T1 - Neutrophil proteinases in hydrochloric acid- and endotoxin-induced acute lung injury
T2 - Evaluation of interstitial protease activity by in situ zymography
AU - Van de Louw, Andry
AU - Jean, Daniel
AU - Frisdal, Eric
AU - Cerf, Charles
AU - d’ortho, Marie Pia
AU - Baker, Andrew H.
AU - Lafuma, Chantal
AU - Duvaldestin, Philippe
AU - Harf, Alain
AU - Delclaux, Christophe
PY - 2002/2
Y1 - 2002/2
N2 - We investigate the role of polymorphonuclear neutrophil (PMN) proteinases, elastase, and gelatinase B in rat models of acute lung injury. Three groups of rats were studied after 6 hours after unilateral instillation of hydrochloric acid (HCl; 0.1 N), lipopolysaccharide (LPS) (4 μg), or saline. The results demonstrated that HCl-induced lung injury as compared with LPS-induced lung injury, was associated with an increase in permeability (wet/dry weight ratio and proteins in bronchoalveolar lavage fluid). In contrast, there was similar PMN recruitment (in bronchoalveolar lavage fluid and myeloperoxidase activity in lung homogenates) and similar proteinase exocytosis residual alveolar PMN content of elastase and gelatinase B) in both types of lung injury. In situ zymography, evaluating interstitial protease/inhibitor balance, demonstrated a decrease in gelatinolytic activity in both HCl and LPS-injured lungs compared with normal lung. The increase in interleukin 6 concentration in lung homogenates, which is observed after both injuries compared with saline-instilled animals, could be involved in up-regulation of tissue inhibitor of matrix metalloproteinase-1, shown by immunocytochemistry to participate in antiproteinase excess. Neither inhibition of alveolar neutrophil influx using leukocyte elastase inhibitor (EPI-hNE-4) nor inhibition of gelatinase activities by recombinant adenovirus for the human tissue inhibitor of matrix metalloproteinase-1 gene transfer decreased lung edema in HCl-induced injury. These data suggest the PMN proteinase do not contribute to HCl-induced acute lung injury in rats.
AB - We investigate the role of polymorphonuclear neutrophil (PMN) proteinases, elastase, and gelatinase B in rat models of acute lung injury. Three groups of rats were studied after 6 hours after unilateral instillation of hydrochloric acid (HCl; 0.1 N), lipopolysaccharide (LPS) (4 μg), or saline. The results demonstrated that HCl-induced lung injury as compared with LPS-induced lung injury, was associated with an increase in permeability (wet/dry weight ratio and proteins in bronchoalveolar lavage fluid). In contrast, there was similar PMN recruitment (in bronchoalveolar lavage fluid and myeloperoxidase activity in lung homogenates) and similar proteinase exocytosis residual alveolar PMN content of elastase and gelatinase B) in both types of lung injury. In situ zymography, evaluating interstitial protease/inhibitor balance, demonstrated a decrease in gelatinolytic activity in both HCl and LPS-injured lungs compared with normal lung. The increase in interleukin 6 concentration in lung homogenates, which is observed after both injuries compared with saline-instilled animals, could be involved in up-regulation of tissue inhibitor of matrix metalloproteinase-1, shown by immunocytochemistry to participate in antiproteinase excess. Neither inhibition of alveolar neutrophil influx using leukocyte elastase inhibitor (EPI-hNE-4) nor inhibition of gelatinase activities by recombinant adenovirus for the human tissue inhibitor of matrix metalloproteinase-1 gene transfer decreased lung edema in HCl-induced injury. These data suggest the PMN proteinase do not contribute to HCl-induced acute lung injury in rats.
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U2 - 10.1038/labinvest.3780406
DO - 10.1038/labinvest.3780406
M3 - Article
C2 - 11850527
AN - SCOPUS:0036169185
SN - 0023-6837
VL - 82
SP - 133
EP - 145
JO - Laboratory Investigation
JF - Laboratory Investigation
IS - 2
ER -