Inhibition of matrix metalloproteinase-9 prevents neutrophilic inflammation in ventilator-induced lung injury

Hyeong Kim Je, Hyun Suk Min, Wui Yoon Dae, Heon Lee Seung, Young Hur Gyu, Hwan Jung Ki, Cheol Jeong Hae, Yong Lee Sung, Yeub Lee Sang, Bum Suh In, Chol Shin, Jeong Shim Jae, Ho In Kwang, Hwa Yoo Se, Kyung Ho Kang

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89 Citations (Scopus)

Abstract

Neutrophils are considered to play a central role in ventilator-induced lung injury (VILI). However, the pulmonary consequences of neutrophil accumulation have not been fully elucidated. Matrix metalloproteinase-9 (MMP-9) had been postulated to participate in neutrophil transmigration. The purpose of this study was to investigate the role of MMP-9 in the neutrophilic inflammation of VILI. Male Sprague-Dawley rats were divided into three groups: 1) low tidal volume (LVT), 7 ml/kg of tidal volume (VT); 2) high tidal volume (HVT), 30 ml/kg of VT; and 3) HVT with MMP inhibitor (HVT+MMPI). As a MMPI, CMT-3 was administered daily from 3 days before mechanical ventilation. Degree of VILI was assessed by wet-to-dry weight ratio and acute lung injury (ALI) scores. Neutrophilic inflammation was determined from the neutrophil count in the lung tissue and myeloperoxidase (MPO) activity in the bronchoalveolar lavage fluid (BALF). MMP-9 expression and activity were examined by immunohistochemical staining and gelatinase zymography, respectively. The wet-to-dry weight ratio, ALI score, neutrophil infiltration, and MPO activity were increased significantly in the HVT group. However, in the HVT+MMPI group, pretreatment with MMPI decreased significantly the degree of VILI, as well as neutrophil infiltration and MPO activity. These changes correlated significantly with MMP-9 immunoreactivity and MMP-9 activity. Most outcomes were significantly worse in the HVT+MMPI group compared with the LVT group. In conclusion, VILI mediated by neutrophilic inflammation is closely related to MMP-9 expression and activity. The inhibition of MMP-9 protects against the development of VILI through the downregulation of neutrophil-mediated inflammation.

Original languageEnglish
Pages (from-to)L580-L587
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume291
Issue number4
DOIs
Publication statusPublished - 2006

Keywords

  • Mechanical ventilators
  • Metalloproteinase inhibitor
  • Neutrophil

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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  • Cite this

    Je, H. K., Min, H. S., Dae, W. Y., Seung, H. L., Gyu, Y. H., Ki, H. J., Hae, C. J., Sung, Y. L., Sang, Y. L., In, B. S., Shin, C., Jae, J. S., Kwang, H. I., Se, H. Y., & Kang, K. H. (2006). Inhibition of matrix metalloproteinase-9 prevents neutrophilic inflammation in ventilator-induced lung injury. American Journal of Physiology - Lung Cellular and Molecular Physiology, 291(4), L580-L587. https://doi.org/10.1152/ajplung.00270.2005