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) All Versions of this Article: 291/5/L887    most recent 00432.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science 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 ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Li, X. Articles by Uhal, B. D. Search for Related Content PubMed PubMed Citation Articles by Li, X. Articles by Uhal, B. D.

Extravascular sources of lung angiotensin peptide synthesis in idiopathic pulmonary fibrosis

¹Department of Physiology, Michigan State University, East Lansing, Michigan; and ²Servicio de Neumologia, Institut Clinic del Tórax, Hospital Clinic, Universidad de Barcelona; ³Servicio de Anatomía Patológica, and ⁴Departamento de Prologia Experimental, Institut de Investigaciones Biomèdiques, Consejo Superior de Investigaciones Cientificas, Barcelona, Spain

Submitted 10 October 2005 ; accepted in final form 19 June 2006

Previous work from this laboratory demonstrated de novo synthesis of angiotensin (ANG) peptides by apoptotic pulmonary alveolar epithelial cells (AEC) and by lung myofibroblasts in vitro and in bleomycin-treated rats. To determine whether these same cell types also synthesize ANG peptides de novo within the fibrotic human lung in situ, we subjected paraffin sections of normal and fibrotic (idiopathic pulmonary fibrosis, IPF) human lung to immunohistochemistry (IHC) and in situ hybridization to detect ANG peptides and angiotensinogen (AGT) mRNA. These were analyzed both alone and in combination with cell-specific markers of AEC [monoclonal antibody (MAb) MNF-116] and myofibroblasts [-smooth muscle actin (-SMA) MAb] and an in situ DNA end labeling (ISEL) method to detect apoptosis. In normal human lung, IHC detected AGT protein in smooth muscle underlying normal bronchi and vessels, but not elsewhere. Real-time RT-PCR and Western blotting revealed that AGT mRNA and protein were 21-fold and 3.6-fold more abundant, respectively, in IPF lung biopsies relative to biopsies of normal human lung (both P < 0.05). In IPF lung, both AGT protein and mRNA were detected in AEC that double-labeled with MAb MNF-116 and with ISEL, suggesting AGT expression by apoptotic epithelia in situ. AGT protein and mRNA also colocalized to myofibroblast foci detected by -SMA MAb, but AGT mRNA was not detected in smooth muscle. These data are consistent with earlier data from isolated human lung cells in vitro and bleomycin-induced rat lung fibrosis models, and they suggest that apoptotic AEC and myofibroblasts constitute key sources of locally derived ANG peptides in the IPF lung.

lung fibrosis; myofibroblast; alveolar epithelial cells; apoptosis

This article has been cited by other articles:

				M. Molina-Molina, A. Xaubet, X. Li, A. Abdul-Hafez, K. Friderici, K. Jernigan, W. Fu, Q. Ding, J. Pereda, A. Serrano-Mollar, et al. Angiotensinogen gene G-6A polymorphism influences idiopathic pulmonary fibrosis disease progression Eur. Respir. J., October 1, 2008; 32(4): 1004 - 1008. [Abstract] [Full Text] [PDF]

				X. Li, M. Molina-Molina, A. Abdul-Hafez, V. Uhal, A. Xaubet, and B. D. Uhal Angiotensin converting enzyme-2 is protective but downregulated in human and experimental lung fibrosis Am J Physiol Lung Cell Mol Physiol, July 1, 2008; 295(1): L178 - L185. [Abstract] [Full Text] [PDF]