Inhibition of matrix metalloproteinase-9 prevents neutrophilic inflammation in ventilator-induced lung injury
| Autor: | Min Hyun Suk, Hae Cheol Jeong, Je Hyeong Kim, Ki Hwan Jung, In Bum Suh, Gyu Young Hur, Seung Heon Lee, Sung Yong Lee, Jae Jeong Shim, Kyung Ho Kang, Chol Shin, Kwang Ho In, Dae Wui Yoon, Se Hwa Yoo, Sang Yeub Lee |
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| Rok vydání: | 2006 |
| Předmět: |
Lung Diseases
Male Pulmonary and Respiratory Medicine Physiology Matrix Metalloproteinase Inhibitors Neutrophilic inflammation Lung injury Matrix (biology) Severity of Illness Index Rats Sprague-Dawley Mechanical ventilator Physiology (medical) Tidal Volume Animals Medicine Enzyme Inhibitors Lung Peroxidase Ventilators Mechanical Staining and Labeling business.industry Matrix metalloproteinase 9 Lung Injury Organ Size Pneumonia Cell Biology respiratory system Immunohistochemistry Rats respiratory tract diseases Matrix Metalloproteinase 9 Neutrophil Infiltration Tetracyclines Immunology Metalloproteinase inhibitor business Bronchoalveolar Lavage Fluid |
| Zdroj: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 291:L580-L587 |
| ISSN: | 1522-1504 1040-0605 |
| DOI: | 10.1152/ajplung.00270.2005 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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