Journal of Biomedical Science

, Volume 15, Issue 4, pp 499–507

The involvement of nitric oxide, nitric oxide synthase, neutrophil elastase, myeloperoxidase and proinflammatory cytokines in the acute lung injury caused by phorbol myristate acetate

  • Yi-Ling Yang
  • Kun-Lun Huang
  • Huey-Ling Liou
  • Hsing I. Chen
Original paper

DOI: 10.1007/s11373-008-9238-y

Cite this article as:
Yang, Y., Huang, K., Liou, H. et al. J Biomed Sci (2008) 15: 499. doi:10.1007/s11373-008-9238-y


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 μg/g lung weight) was added into the lung perfusate. Vehicle group received dimethyl sulfoxide (the solvent for PMA) 100 μg/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.


Acute lung injuryPhorbol myristate acetateInducible nitric oxide synthaseNeutrophil elastaseMyeloperoxidaseProinflammatory cytokines

Copyright information

© National Science Council Taipei 2008

Authors and Affiliations

  • Yi-Ling Yang
    • 1
  • Kun-Lun Huang
    • 2
  • Huey-Ling Liou
    • 3
  • Hsing I. Chen
    • 4
  1. 1.Institute of BiotechnologyNational Chia-Yi UniversityChiayiTaiwan
  2. 2.Institute of Undersea and Hyperbaric MedicineNational Defense Medical CenterTaipeiTaiwan
  3. 3.Department of NursingTaipei Veteran General HospitalTaipeiTaiwan
  4. 4.Institute of Integrative Physiology and Clinical Sciences and of Medical SciencesTzu Chi UniversityHualienTaiwan