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 Ryter, S. W. Articles by Choi, A. M. K. Search for Related Content PubMed PubMed Citation Articles by Ryter, S. W. Articles by Choi, A. M. K.

Autophagy in the Lung

¹ Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts

Correspondence and requests for reprints should be addressed to Stefan W. Ryter, Ph.D., Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115. E-mail: sryter{at}partners.org

ABSTRACT

Autophagy is a cellular process for the disposal of damaged organelles or denatured proteins through a lysosomal degradation pathway. By reducing endogenous macromolecules to their basic components (i.e., amino acids, lipids), autophagy serves a homeostatic function by ensuring cell survival during starvation. Increased autophagy can be found in dying cells, although the relationships between autophagy and programmed cell death remain unclear. To date, few studies have examined the regulation and functional significance of autophagy in human lung disease. The lung, a complex organ that functions primarily in gas exchange, consists of diverse cell types (i.e., endothelial, epithelial, mesenchymal, inflammatory). In lung cells, autophagy may represent a general inducible adaptive response to injury resulting from exposure to stress agents, including hypoxia, oxidants, inflammation, ischemia–reperfusion, endoplasmic reticulum stress, pharmaceuticals, or inhaled xenobiotics (i.e., air pollution, cigarette smoke). In recent studies, we have observed increased autophagy in mouse lungs subjected to chronic cigarette smoke exposure, and in pulmonary epithelial cells exposed to cigarette smoke extract. Knockdown of autophagic proteins inhibited apoptosis in response to cigarette smoke exposure in vitro, suggesting that increased autophagy was associated with epithelial cell death. We have also observed increased morphological and biochemical markers of autophagy in human lung specimens from patients with chronic obstructive pulmonary disease (COPD). We hypothesize that increased autophagy contributes to COPD pathogenesis by promoting epithelial cell death. Further research will examine whether autophagy plays a homeostatic or maladaptive role in COPD and other human lung diseases.

Key Words: autophagy • apoptosis • pulmonary disease

This article has been cited by other articles:

				S. W. Ryter, S.-J. Lee, A. Smith, and A. M. K. Choi Autophagy in Vascular Disease Proceedings of the ATS, February 15, 2010; 7(1): 40 - 47. [Abstract] [Full Text] [PDF]