AJP - Lung Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Lung Cell Mol Physiol 286: L801-L807, 2004. First published November 26, 2003; doi:10.1152/ajplung.00335.2003
1040-0605/04 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
286/4/L801    most recent
00335.2003v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (17)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lian, X.
Right arrow Articles by Du, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lian, X.
Right arrow Articles by Du, H.

Lysosomal acid lipase deficiency causes respiratory inflammation and destruction in the lung

Xuemei Lian,1,4 Cong Yan,2,3 Li Yang,2 Yan Xu,2 and Hong Du1

1Division of Human Genetics, 2Division of Pulmonary Biology, and 3Graduate Program for Molecular and Developmental Biology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039; and 4Graduate Program for Pediatrics, Chongqing University of Medical Sciences, Chongqing 400016, China

Submitted 18 September 2003 ; accepted in final form 19 November 2003

The functional roles of neutral lipids are poorly understood in the lung. Blocking cholesteryl ester and triglyceride metabolism in lysosomal acid lipase gene knockout mice (lal-/-) resulted in a high level of neutrophil influx in the lungs as early as 2 mo of age. Bronchoalveolar macrophages appeared foamy and gradually increased in number with age progression. Affymetrix GeneChip array analysis of lung mRNA showed increased levels of proinflammatory cytokine (including IL-1{beta}, IL-6, and TNF-{alpha}) and matrix metalloproteinase (including MMP-8, MMP-9, and MMP-12) expression in lal-/- mice. With age progression, some areas of lal-/- mice developed severe abnormal cell proliferation and alveolar remodeling. In other areas, alveolar destruction (i.e., emphysema) was observed. In addition, Clara cell hypertrophy and hyperplasia developed in conducting airways. The pathophysiological phenotypes in the lal-/- mouse lungs became more severe with increasing age. The studies support the concept that neutral lipid metabolites play essential roles in pulmonary homeostasis, inflammatory responses, remodeling, and injury repair.

neutral lipid; remodeling; emphysema


Address for reprint requests and other correspondence: H. Du, Div. of Human Genetics, and C. Yan, Div. of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH 45229-3039 (E-mail: Hong.Du{at}cchmc.org and Cong.Yan{at}cchmc.org).




This article has been cited by other articles:


Home page
 J. Lipid Res.Home page
H. Du, T. L. Cameron, S. J. Garger, G. P. Pogue, L. A. Hamm, E. White, K. M. Hanley, and G. A. Grabowski
Wolman disease/cholesteryl ester storage disease: efficacy of plant-produced human lysosomal acid lipase in mice
J. Lipid Res., August 1, 2008; 49(8): 1646 - 1657.
[Abstract] [Full Text] [PDF]

Home page
 Proc Am Thorac SocHome page
A. Sharafkhaneh, N. A. Hanania, and V. Kim
Pathogenesis of Emphysema: From the Bench to the Bedside
Proceedings of the ATS, May 1, 2008; 5(4): 475 - 477.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
Y. Li, H. Du, Y. Qin, J. Roberts, O. W. Cummings, and C. Yan
Activation of the Signal Transducers and Activators of the Transcription 3 Pathway in Alveolar Epithelial Cells Induces Inflammation and Adenocarcinomas in Mouse Lung
Cancer Res., September 15, 2007; 67(18): 8494 - 8503.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. Baldan, P. Tarr, C. S. Vales, J. Frank, T. K. Shimotake, S. Hawgood, and P. A. Edwards
Deletion of the Transmembrane Transporter ABCG1 Results in Progressive Pulmonary Lipidosis
J. Biol. Chem., September 29, 2006; 281(39): 29401 - 29410.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
C. Yan, X. Lian, Y. Li, Y. Dai, A. White, Y. Qin, H. Li, D. A. Hume, and H. Du
Macrophage-Specific Expression of Human Lysosomal Acid Lipase Corrects Inflammation and Pathogenic Phenotypes in lal-/- Mice
Am. J. Pathol., September 1, 2006; 169(3): 916 - 926.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
D. M. Simon, M. C. Arikan, S. Srisuma, S. Bhattacharya, L. W. Tsai, E. P. Ingenito, F. Gonzalez, S. D. Shapiro, and T. J. Mariani
Epithelial cell PPAR{gamma} contributes to normal lung maturation
FASEB J, July 1, 2006; 20(9): 1507 - 1509.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
E. L. Martin, L. A. McCaig, B. Z. Moyer, M. C. Pape, K. J. Leco, J. F. Lewis, and R. A. W. Veldhuizen
Differential response of TIMP-3 null mice to the lung insults of sepsis, mechanical ventilation, and hyperoxia
Am J Physiol Lung Cell Mol Physiol, August 1, 2005; 289(2): L244 - L251.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
C. Yan and H. Du
Alveolus formation: what have we learned from genetic studies?
J Appl Physiol, October 1, 2004; 97(4): 1543 - 1548.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2004 by the American Physiological Society.