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Can Retinoic Acid Ameliorate the Physiologic and Morphologic Effects of Elastase Instillation in the Rat?*

Jeffrey Tepper, PhD; Juergen Pfeiffer, MS; Melinda Aldrich, BS; Daniel Tumas, DVM, PhD; Jeffrey Kern, MD, FCCP; Eric Hoffman, PhD; Geoffrey McLennan, MD; Dallas Hyde, PhD
Author and Funding Information

*From Genentech, Inc (Drs. Tepper and Tumas, Mr. Pfeiffer, Ms. Aldrich), South San Francisco, CA; the University of Iowa (Drs. Kern, Hoffman, and McLennan), School of Medicine, Iowa City, IA; and the University of California (Dr. Hyde), Davis, CA.

Correspondence to: Jeffrey Tepper, PhD, Immunology Research, MS-34, Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080



Chest. 2000;117(5_suppl_1):242S-244S. doi:10.1378/chest.117.5_suppl_1.242S
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Abbreviations: Dlco = diffusing capacity of the lung for carbon monoxide; FRC = functional residual capacity; RA = retinoic acid

Emphysema is a chronic obstructive lung disease that is characterized by enlarged airspaces and is accompanied by alveolar destruction. It is generally thought that alveoli, once damaged, cannot be repaired in the adult lung. However, compensatory lung growth with increased complexity of alveolar septa in adult dogs was reported1 after 54% of their lung was removed (right pneumonectomy), a finding that was not reported when 42% of their lung was removed (left pneumonectomy). This study suggested that given the appropriate signal(s), the lung might be capable of growing new alveoli. The growth of new alveoli also was reported in postnatal rats treated with systemic retinoic acid (RA) after the suppression of alveolar growth by dexamethasone.2 However, the necessary components for alveolar septation are available in young rats. More recently, new alveolar growth was reported in adult rats that had been treated systemically with RA after intratracheal elastase-induced destruction of alveoli.3 We asked whether the finding of new alveolar septation after RA treatment could be replicated and whether this repair produced an improvement in the lung function of rats whose lungs were damaged by elastase instillation, which is a model of emphysema.

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