help button home button
AJRCCM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Published ahead of print on August 27, 2004, doi:10.1164/rccm.200402-146OC
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Online Supplement
Right arrow All Versions of this Article:
200402-146OCv1
170/11/1239    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Goto, T.
Right arrow Articles by Kobayashi, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Goto, T.
Right arrow Articles by Kobayashi, K.
American Journal of Respiratory and Critical Care Medicine Vol 170. pp. 1239-1246, (2004)
© 2004 American Thoracic Society
doi: 10.1164/rccm.200402-146OC

Original Article

Importance of Tumor Necrosis Factor-{alpha} Cleavage Process in Post-Transplantation Lung Injury in Rats

Taichiro Goto, Akitoshi Ishizaka, Fujio Kobayashi, Mitsutomo Kohno, Makoto Sawafuji, Sadatomo Tasaka, Eiji Ikeda, Yasunori Okada, Ikuro Maruyama and Koichi Kobayashi

Departments of Surgery, Medicine, and Pathology, School of Medicine, Keio University, Tokyo; Research & Development Division, Mitsubishi Pharma Corporation, Yokohama; and Department of Laboratory and Molecular Medicine, Faculty of Medicine, Kagoshima University, Kagoshima, Japan

Correspondence and requests for reprints should be addressed to Akitoshi Ishizaka, M.D., Department of Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160–8582, Japan. E-mail: ishizaka{at}cpnet.med.keio.ac.jp

Tumor necrosis factor-{alpha} (TNF-{alpha}) has two forms with apparently different biological activities: a membrane-associated form and a soluble form. TNF-{alpha}–converting enzyme (TACE) mediates a cleavage of membrane-associated TNF-{alpha} to induce its bioactive soluble form. We hypothesized that inhibition of TACE might prevent TNF-{alpha}–induced tissue injury while preserving the benefits of TNF-{alpha}. In this study, we evaluated the role of TACE in acute inflammation using an inhibitor of the enzyme in a rat model of lung transplantation. Inbred Lewis rats underwent left lung isotransplantation, and the donor lungs were kept in Euro-Collins solution with or without the inhibitor. After 6 hours of ischemia, the left lung was transplanted into the recipient rat and reperfused for 4 hours. Inhibition of TACE significantly attenuated endothelial and alveolar septal damage, as assessed by radiolabeled albumin leakage after transplantation. The inhibition also attenuated neutrophil accumulation in the alveolar space and other histopathologic findings, including intercellular adhesion molecule-1 expression. In addition, significantly lower levels of monocyte chemotactic protein-1, cytokine-induced neutrophil chemoattractant-1, high mobility group box-1, and soluble epithelial cadherin and decreased neutrophil elastase activity were observed in bronchoalveolar lavage fluid from the rats treated with the inhibitor. We conclude that TACE mediates a critical step in the development of post-transplantation lung injury.

Key Words: acute inflammation • epithelial cadherin • high mobility group box-1 • lung transplantation • TNF-{alpha}–converting enzyme




This article has been cited by other articles:


Home page
 ICVTSHome page
A. Tajima, M. Kohno, M. Watanabe, Y. Izumi, S. Tasaka, I. Maruyama, T. Miyasho, and K. Kobayashi
Occult injury in the residual lung after pneumonectomy in mice
Interactive CardioVascular and Thoracic Surgery, December 1, 2008; 7(6): 1114 - 1120.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
A. Thammanomai, A. Majumdar, E. Bartolak-Suki, and B. Suki
Effects of reduced tidal volume ventilation on pulmonary function in mice before and after acute lung injury
J Appl Physiol, November 1, 2007; 103(5): 1551 - 1559.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
M. Zhao, L. G. Fernandez, A. Doctor, A. K. Sharma, A. Zarbock, C. G. Tribble, I. L. Kron, and V. E. Laubach
Alveolar macrophage activation is a key initiation signal for acute lung ischemia-reperfusion injury
Am J Physiol Lung Cell Mol Physiol, November 1, 2006; 291(5): L1018 - L1026.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
H. Liu, L. Liu, B. S. Fletcher, and G. A. Visner
Novel Action of Indoleamine 2,3-Dioxygenase Attenuating Acute Lung Allograft Injury
Am. J. Respir. Crit. Care Med., March 1, 2006; 173(5): 566 - 572.
[Abstract] [Full Text] [PDF]

Home page
 J. Thorac. Cardiovasc. Surg.Home page
H. Liu, P. Drew, Y. Cheng, and G. A. Visner
Pirfenidone inhibits inflammatory responses and ameliorates allograft injury in a rat lung transplant model
J. Thorac. Cardiovasc. Surg., September 1, 2005; 130(3): 852 - 858.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
T. D. Bradley, Y. E. Miller, F. J. Martinez, D. C. Angus, W. MacNee, and E. Abraham
Interstitial Lung Disease, Lung Cancer, Lung Transplantation, Pulmonary Vascular Disorders, and Sleep-disordered Breathing in AJRCCM in 2004
Am. J. Respir. Crit. Care Med., April 1, 2005; 171(7): 675 - 685.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Cell Mol. Biol.
Copyright © 2004 American Thoracic Society 		  ATS Conference