HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Voelkel, N. Articles by Taraseviciene-Stewart, L. Search for Related Content PubMed PubMed Citation Articles by Voelkel, N. Articles by Taraseviciene-Stewart, L.

Emphysema

An Autoimmune Vascular Disease?

COPD Center, Pulmonary and Critical Care Medicine Division, University of Colorado Health Sciences Center, Denver, Colorado

Correspondence and requests for reprints should be addressed to: Norbert F. Voelkel, M.D., Division of Pulmonary Sciences and Critical Care Medicine, 4200 East Ninth Avenue, C272, Denver, CO 80262. E-mail: norbert.voelkel{at}uchsc.edu

We propose that an endogenous maintenance program controls lung cell turnover, apoptosis, and tissue repair, and that emphysema is a manifestation of the breakdown of the lung structure maintenance program. Emphysema can be induced experimentally in rats by three methods: blockade of vascular endothelial growth factor receptors using SU5416, a small molecule–tyrosine kinase inhibitor; methylprednisolone, which activates matrix metalloproteinase-9 and decreases Akt phosphorylation; and antibodies directed against endothelial cells (autoimmune emphysema). SU5416-induced emphysema is associated with lung induction of cytochrome P450 and oxidant stress, and a superoxide dismutase mimetic or N-acetylcysteine prevents this form of emphysema. A broad-spectrum metalloproteinase inhibitor prevents methylprednisolone-induced emphysema and, finally, autoimmune emphysema is associated with increased lung tissue metalloproteinase-9 expression and alveolar septal cell apoptosis. Athymic rats, which lack CD4+ T cells, are protected against autoimmune emphysema, whereas adoptive transfer of CD4+ T cells causes autoimmune emphysema in naive adult rats. It appears that vascular endothelial growth factor and signaling via its receptors plays a central role in the lung structural maintenance program, and oxidative stress, proteolysis, and apoptosis may coincide in the moment of lung cell destruction. Interestingly, the methylprednisolone model illustrates that inflammation is not necessary for the development of emphysema.

Key Words: autoimmune disease • emphysema • metalloproteinase-9 • methylprednisolone • vascular endothelial growth factor

This article has been cited by other articles:

				V. I. Peinado, S. Pizarro, and J. A. Barbera Pulmonary Vascular Involvement in COPD Chest, October 1, 2008; 134(4): 808 - 814. [Abstract] [Full Text] [PDF]

				C. A. Feghali-Bostwick, A. S. Gadgil, L. E. Otterbein, J. M. Pilewski, M. W. Stoner, E. Csizmadia, Y. Zhang, F. C. Sciurba, and S. R. Duncan Autoantibodies in Patients with Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., January 15, 2008; 177(2): 156 - 163. [Abstract] [Full Text] [PDF]

				N. F. Voelkel, I. S. Douglas, and M. Nicolls Angiogenesis in Chronic Lung Disease Chest, March 1, 2007; 131(3): 874 - 879. [Abstract] [Full Text] [PDF]

				L. Taraseviciene-Stewart, I. S. Douglas, P. S. Nana-Sinkam, J. D. Lee, R. M. Tuder, M. R. Nicolls, and N. F. Voelkel Is Alveolar Destruction and Emphysema in Chronic Obstructive Pulmonary Disease an Immune Disease? Proceedings of the ATS, November 1, 2006; 3(8): 687 - 690. [Abstract] [Full Text] [PDF]

				J Vestbo and J C Hogg Convergence of the epidemiology and pathology of COPD Thorax, January 1, 2006; 61(1): 86 - 88. [Abstract] [Full Text] [PDF]