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(Chest. 2006;129:1673-1682.)
© 2006 American College of Chest Physicians

Burying the Dead*

The Impact of Failed Apoptotic Cell Removal (Efferocytosis) on Chronic Inflammatory Lung Disease

R. William Vandivier, MD; Peter M. Henson, PhD and Ivor S. Douglas, MD

* From the COPD Center (Dr. Vandivier) and the Division of Pulmonary Sciences and Critical Care Medicine (Dr. Douglas), University of Colorado at Denver Health Sciences Center; and the Department of Immunology (Dr. Henson), National Jewish Medical and Research Center, Denver, CO.

Correspondence to: R. William Vandivier, MD, University of Colorado at Denver Health Sciences Center, COPD Center, Division of Pulmonary Sciences and Critical Care Medicine, 4200 E Ninth Ave, Box C272, Denver, CO 80220; e-mail: Bill.Vandivier{at}uchsc.edu

Abstract

Apoptosis and the removal of apoptotic cells (termed efferocytosis) are tightly coupled with the regulation of normal lung structure, both in the developing and adult organism. Processes that disrupt or uncouple this balance have the potential to alter normal cell turnover, ultimately resulting in the induction of lung pathology and disease. Apoptotic cells are increased in several chronic inflammatory lung diseases, including cystic fibrosis (CF), non-CF bronchiectasis, COPD, and asthma. While this may well be due to the enhanced induction of apoptosis, increasing data suggest that the clearance of dying cells is also impaired. Because efferocytosis appears to be a key regulatory checkpoint for the innate immune system, the adaptive immune system, and cell proliferation, the failure of this highly conserved process may contribute to disease pathogenesis by impeding both the resolution of inflammation and the maintenance of alveolar integrity. The recognition of impaired efferocytosis as a contributor to chronic inflammation may ultimately direct us toward the identification of new disease biomarkers, as well as novel therapeutic approaches.

Key Words: asthma • COPD • cystic fibrosis






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Copyright © 2006 by the American College of Chest Physicians.