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© 2006 The American Thoracic Society
doi: 10.1513/pats.200605-105SF
Is Alveolar Destruction and Emphysema in Chronic Obstructive Pulmonary Disease an Immune Disease?
Pulmonary and Critical Care Medicine Division, University of Colorado at Denver and Health Sciences Center, Denver, Colorado; and Cardiopulmonary Pathology Division, Department of Pathology, Johns Hopkins University, Baltimore, Maryland
Correspondence and requests for reprints should be addressed to Norbert F. Voelkel, M.D., University of Colorado Health Sciences Center, 4200 East Ninth Avenue, BRB, Room 621, Mail Stop: C272, Denver, CO 80262. E-mail: norbert.voelkel{at}uchsc.edu
ABSTRACT
The alveolar destruction leading to airspace enlargement in patients with end-stage chronic obstructive pulmonary disease (COPD) is frequently progressive, despite smoking cessation. Several laboratories have accumulated data demonstrating the presence of immune cells in bronchial biopsy specimens and lung tissue sections from patients with COPD. Recently, the accumulation of T and B lymphocytes, often forming follicles, in the lung parenchyma from patients with severe COPD has been reported. In addition, it has been postulated that there might be an autoimmune component to COPD. T-cell receptor analysis has provided data consistent with the concept of T-cell clones in the lung tissue from patients with COPD. Against this background, we developed a model of autoimmune emphysema in adult rats. Based on published data showing that immunization of mice with human umbilical vein endothelial cells (HUVECs) causes production of anti–vascular endothelial growth factor (VEGF) receptor II (KDR) antibodies, and our own data indicating that administration of a VEGF receptor blocker in adult rats causes emphysema, we reasoned that intraperitoneal injection of HUVECs in rats would generate both anti-VEGF receptor antibodies and emphysema. Indeed, intraperitoneal injection of HUVECs caused emphysema. We further explored the autoimmune nature of this model, identified KDR antibodies in the serum of HUVEC-immunized rats, and injected serum from the emphysematous rats into naive rats and mice, which resulted in emphysema. Presently, we are in the process of investigating whether cigarette smoke extract causes emphysema. We recently identified anti–endothelial cell antibodies in the serum of patients with end-stage emphysema.
Key Words: emphysema • apoptosis • autoimmune disease
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