The involvement of nitric oxide, nitric oxide synthase, neutrophil elastase, myeloperoxidase and proinflammatory cytokines in the acute lung injury caused by phorbol myristate acetate.
Phorbol myristate acetate (PMA) causes acute lung injury (ALI). The present study was designed to elucidate the role of nitric oxide (NO), inducible NO synthase (iNOS), neutrophil elastase (NE) and other mediators in the ALI caused by PMA. In isolated rat's lungs, PMA at various doses (1, 2 and 4 mug/g lung weight) was added into the lung perfusate. Vehicle group received dimethyl sulfoxide (the solvent for PMA) 100 mug/g. We measured the lung weight changes, pulmonary arterial pressure, capillary filtration coefficient, exhaled NO, protein concentration in bronchoalveolar lavage (PCBAL) and Evan blue dye leakage. Nitrate/nitrite, methyl guanidine, proinflammatory cytokines, NE and myeloperoxidase (MPO) in lung perfusate were determined. Histopathological examination was performed. We detected the iNOS mRNA expression in lung tissue. PMA caused dose-dependent increases in variables for lung changes, and nitrate/nitrite, methyl guanidine, proinflammatory cytokines, NE and MPO in lung perfusate. The pathology was characterized by alveolar hemorrhagic edema with inflammatory cell infiltration. Scanning electron microscopy revealed endothelial damage. PMA upregulated the expression of iNOS mRNA. Our results suggest that neutrophil activation by PMA causes release of NE, upregulation of iNOS and a series of inflammatory responses leading to endothelial damage and ALI.
Yang
Yi-Ling
YL
Institute of Biotechnology, National Chia-Yi University, Chiayi, Taiwan.
Huang
Kun-Lun
KL
Liou
Huey-Ling
HL
Chen
Hsing I
HI
D000818:Animals; D016207:Cytokines / Q000502:physiology*; D066298:In Vitro Techniques; D007249:Inflammation; D019272:Leukocyte Elastase / Q000378:metabolism* / Q000502:physiology; D008168:Lung; D008297:Male; D018375:Neutrophil Activation; D009569:Nitric Oxide / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics* / Q000502:physiology; D009195:Peroxidase / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000209:etiology* / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000493:pharmacokinetics
D016207:Cytokines; D012333:RNA, Messenger; D009569:Nitric Oxide; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D019272:Leukocyte Elastase; D013755:Tetradecanoylphorbol Acetate