|
|
Prepublished online as a Blood First Edition Paper on April 10, 2003; DOI 10.1182/blood-2002-07-2135.
 Previous Article | Table of Contents | Next Article 
Blood, 1 August 2003, Vol. 102, No. 3, pp. 1087-1096
RED CELLS
Inhaled nitric oxide protects transgenic SAD mice from sickle cell disease–specific lung injury induced by hypoxia/reoxygenation
Lucia de Franceschi,
Antonella Baron,
Aldo Scarpa,
Christophe Adrie,
Anne Janin,
Stefano Barbi,
Jean Kister,
Philippe Rouyer-Fessard,
Roberto Corrocher,
Philippe Leboulch, and
Yves Beuzard
From the Department of Clinical and Experimental Medicine, Section of Internal Medicine, University of Verona; Department of Pathology, Section of Anatomic Pathology, University of Verona, Italy; Laboratory of Hematopoietic Gene Therapy, Hopital St Louis; Laboratoire de Pathologie, Institute National de la Santé et de la Recherche Médicale (INSERM) 02 20, Hopital Saint Louis, Paris; INSERM Unit 473, Bicetre Hopital, Le Kremlin Bicetre, France; Division of Health Sciences & Technology, Massachusetts Institute of Technology, Cambridge; and Harvard Medical School and Division of Genetics, Department of Medicine, Brigham & Women's Hospital, Boston, MA
Central to the pathophysiology of sickle cell disease are the vaso-occlusive events that lead to tissue damages and life-threatening complications. Lungs are particularly vulnerable to vaso-occlusion because of their specific vasculature. We developed a mouse model of hypoxia/reoxygenation lung injury closely mimicking the lung pathology of patients with sickle cell disease. This model involves the exposure of transgenic sickle cell (SAD) mice to hypoxia (8% oxygen) for 4, 10, and 46 hours followed by 2 hours of reoxygenation. Gene expression profiling of SAD lung tissue pointed to the specific induction of genes involved in the response to ischemic stress and microcirculation remodeling: Hspcb, Hsp86-1, Nfe2l2, Ace, and Fgf7. Hypoxia/reoxygenation also induced a marked increase in bronchoalveolar (BAL) total leukocyte and neutrophil counts, BAL total protein content, and BAL tumor necrosis factor  (TNF-), interleukin 6 (IL-6), IL-1, and macrophage inflammatory protein 2 (MIP-2) levels, all indicators of enhanced inflammatory response as compared with control mice. Nitric oxide (NO) was administered to SAD mice. NO (40 ppm) inhalation protected SAD mice from the histopathologic lesions of ischemic/reperfusion lung injury with corresponding normalization and/or modulation of tissue gene expression profiles. Inhaled NO (1) significantly reduced the increase in BAL total protein content, BAL total leukocyte, and neutrophil counts; (2) modulated BAL cytokine network; and (3) did not affect hemoglobin and methemoglobin levels. The present study provides evidences for the beneficial effects of inhaled NO in pulmonary injury induced by hypoxia/reoxygenation in a mouse model of sickle cell disease (SCD) and opens new avenues in drug design based on tissue gene expression profiling.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
L. De Franceschi, O. S. Platt, G. Malpeli, A. Janin, A. Scarpa, C. Leboeuf, Y. Beuzard, E. Payen, and C. Brugnara
Protective effects of phosphodiesterase-4 (PDE-4) inhibition in the early phase of pulmonary arterial hypertension in transgenic sickle cell mice
FASEB J,
June 1, 2008;
22(6):
1849 - 1860.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. S. Kim, V. Rajagopal, C. Gonsalves, C. Johnson, and V. K. Kalra
A Novel Role of Hypoxia-Inducible Factor in Cobalt Chloride- and Hypoxia-Mediated Expression of IL-8 Chemokine in Human Endothelial Cells
J. Immunol.,
November 15, 2006;
177(10):
7211 - 7224.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. de Franceschi, G. Malpeli, A. Scarpa, A. Janin, E. M. Muchitsch, P. Roncada, C. Leboeuf, R. Corrocher, Y. Beuzard, and C. Brugnara
Protective effects of S-nitrosoalbumin on lung injury induced by hypoxia-reoxygenation in mouse model of sickle cell disease
Am J Physiol Lung Cell Mol Physiol,
September 1, 2006;
291(3):
L457 - L465.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. J. McMahon and A. Doctor
Extrapulmonary effects of inhaled nitric oxide: role of reversible s-nitrosylation of erythrocytic hemoglobin.
Proceedings of the ATS,
January 1, 2006;
3(2):
153 - 160.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. De Franceschi, G. Malpeli, A. Janin, E. Muchitsch, A. Scarpa, P. Leboulch, C. Leboeuf, Y. Beuzard, and C. Brugnara
Protective Effects of No-Albumin and Albumin on Lung Injury Induced by Hypoxia/Reoxygenation in a Mouse Model of Sickle Cell Disease.
Blood (ASH Annual Meeting Abstracts),
November 16, 2004;
104(11):
3580 - 3580.
[Abstract]
|
|
|
|
|
|
|
A. Solovey, R. Kollander, A. Shet, L. C. Milbauer, S. Choong, A. Panoskaltsis-Mortari, B. R. Blazar, R. J. Kelm Jr, and R. P. Hebbel
Endothelial cell expression of tissue factor in sickle mice is augmented by hypoxia/reoxygenation and inhibited by lovastatin
Blood,
August 1, 2004;
104(3):
840 - 846.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
