Patients With COPD Evidence for Apoptosis in the ...

Expression of 15-Lipoxygenase and Evidence for Apoptosis in the Lungs From Patients With COPD* Yasunori Kasahara, Rubin M. Tuder, Carlyne D. Cool and Norbert F. Voelkel Chest 2000;117;260S DOI 10.1378/chest.117.5_suppl_1.260S The online version of this article, along with updated information and services can be found online on the World Wide Web at: http://chestjournal.chestpubs.org/content/117/5_suppl_1/260S.1.full.html

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Expression of 15-Lipoxygenase and Evidence for Apoptosis in the Lungs From Patients With COPD* Yasunori Kasahara, MD; Rubin M. Tuder, MD; Carlyne D. Cool, MD; Norbert F. Voelkel, MD

(CHEST 2000; 117:260S) Abbreviations: KDR ⫽ kinase insert domain-containing receptor; VEGF ⫽ vascular endothelial growth factor

here is a loss of alveolar structures and endothelial T cells in emphysema. We hypothesize that the disap-

pearance of lung alveoli resulting in emphysema may occur by apoptosis following decreased expression or

*From the Pulmonary Hypertension Center, Department of Medicine (Drs. Kasahara and Voelkel) and Department of Pathology (Drs. Tuder and Cool), University of Colorado Health Sciences Center, Denver, CO. Correspondence to: Yasunori Kashahara, MD, Division of Pulmonary Science and Critical Care Medicine, University of Colorado Health Sciences Center, 4200 E. 9th Ave, Denver, CO 80262 260S

activity of lung vascular endothelial growth factor (VEGF) or its receptor, kinase insert domain-containing receptor(KDR). To examine this hypothesis, we carried out the TUNEL technique in lung samples obtained from 6 patients with emphysema and 11 normal control subjects (7 nonsmokers and 4 smokers). We found an increased number of TUNEL-positive cells/nucleic acids in alveolar septum in emphysema when compared with normal lungs. The cell death events were not different between healthy nonsmokers and nonemphysema smokers. Double staining with TUNEL and cytokeratin or factor VIII-related antigen confirmed endothelial cell and epithelial cell death in emphysema lungs. Western blot analysis for KDR of whole lung protein extracts showed that KDR protein expression was significantly reduced in emphysema lungs. In situ hybridization revealed a focally decreased expression of VEGF and KDR messenger RNA in emphysema lungs. Using immunohistochemistry, we localized and semiquantitatively estimated the abundance of 15-lipoxygenase in lungs obtained from 6 patients with emphysema, 6 normal control subjects, and 7 patients with severe pulmonary hypertension. Expression of 15-lipoxygenase in pulmonary arteries in emphysema was less intense than in severe pulmonary hypertension. We conclude that cell death events occur in emphysema, and that VEGF and its receptor KDR are decreased in emphysema lungs. We speculate that emphysema may occur by apoptosis following decreased expression or activity of lung VEGF or its receptor KDR.

Morphometry Explains Variation in Airway Responsiveness in Transgenic Mice Overexpressing Interleukin-6 and Interleukin-11 in the Lung* Charles Kuhn, MD; Robert J. Homer, MD, PhD; Zhou Zhu, MD, PhD; Nicholas Ward, MD; and Jack A. Elias, MD

(CHEST 2000; 117:260S–262S) Abbreviations: AA ⫽ alveolar wall attached; AHR ⫽ airway hyperreactivity; CC10 ⫽ Clara cell 10-kd protein; IL ⫽ interleukin; S/V ⫽ surface/volume ratio

he basis for airway hyperreactivity (AHR) accompanyT ing COPD is poorly understood. Structural changes

may play a role. We have generated transgenic mice that overexpress related cytokines, interleukin (IL)-6 and IL11, in their airways, which were controlled by the Clara cell 10-kd protein (CC10) promoter. Despite some similar

*From the Department of Pathology (Dr. Kuhn), Brown University School of Medicine, Providence, RI; and the Departments of Pathology (Dr. Homer) and Pulmonary and Critical Care Medicine (Drs. Zhu, Ward, and Elias), Yale University, New Haven, CT. Correspondence to: Charles Kuhn, MD, Pathology Department, Memorial Hospital of Rhode Island, Pawtucket, RI 02860 Thomas L. Petty 42nd Annual Aspen Lung Conference: Mechanisms of COPD


Expression of 15-Lipoxygenase and Evidence for Apoptosis in the Lungs From Patients With COPD * Yasunori Kasahara, Rubin M. Tuder, Carlyne D. Cool and Norbert F. Voelkel Chest 2000;117; 260S DOI 10.1378/chest.117.5_suppl_1.260S This information is current as of April 12, 2012 Updated Information & Services Updated Information and services can be found at: http://chestjournal.chestpubs.org/content/117/5_suppl_1/260S.1.full.html Cited Bys This article has been cited by 3 HighWire-hosted articles: http://chestjournal.chestpubs.org/content/117/5_suppl_1/260S.1.full.html#related-urls Permissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://www.chestpubs.org/site/misc/reprints.xhtml Reprints Information about ordering reprints can be found online: http://www.chestpubs.org/site/misc/reprints.xhtml Citation Alerts Receive free e-mail alerts when new articles cite this article. To sign up, select the "Services" link to the right of the online article. Images in PowerPoint format Figures that appear in CHEST articles can be downloaded for teaching purposes in PowerPoint slide format. See any online figure for directions.
