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: 291/3/L457    most recent 00462.2005v1 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 ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by de Franceschi, L. Articles by Brugnara, C. Search for Related Content PubMed PubMed Citation Articles by de Franceschi, L. Articles by Brugnara, C.

Protective effects of S-nitrosoalbumin on lung injury induced by hypoxia-reoxygenation in mouse model of sickle cell disease

¹Section of Internal Medicine, Department of Clinical and Experimental Medicine, and ²Section of Anatomic Pathology, Department of Pathology, University of Verona, Verona, Italy; ³Laboratorie de Pathologie, Institut National de la Santé et de la Recherche Médicale INSERM 02 20, Hopital Saint Louis, Paris, France; ⁴Department of Experimental Pharmacology, Baxter Bioscience, Vienna, Austria; ⁵Istituto Italiano Spallanzani, Milan, Italy; ⁶Laboratory of Hematopoietic Gene Therapy, INSERM U733, Centre Hayem, Hopital Saint Louis, Paris, France; and ⁷Department of Laboratory Medicine and Department of Pathology, Children's Hospital, Harvard Medical School, Boston, Massachusetts

Submitted 3 November 2005 ; accepted in final form 23 March 2006

Nitric oxide (NO) is a potential new therapeutic agent for sickle cell disease (SCD). We investigated the effects of NO donor on hypoxia-induced acute lung injury that occurs when transgenic sickle cell SAD mice are exposed to chronic hypoxia, a model for lung vasoocclusive sickle cell events. In wild-type and SAD mice, intraperitoneal injection of S-nitrosoalbumin (NO-Alb) produced no significant hematologic changes under room air conditions, whereas it induced mild temporary hypotension and inhibition of platelet aggregation. NO-Alb administration (300 mg/kg ip twice a day, equivalent to 7.5 µM NO) in wild-type and SAD mice exposed to 46 h of hypoxia (8% oxygen) followed by 2 h of normoxia resulted in 1) reduction of the hypoxia-induced increase in blood neutrophil count, 2) prevention of hypoxia-induced increased IL-6 and IL-1 levels in bronchoalveolar lavage, 3) reduction of the lung injury induced by hypoxia-reoxygenation, 4) prevention of thrombus formation, and 5) prevention of hypoxia-induced increase of lung matrix metalloproteinase-9 gene expression. These effects provide new insights into the possible use of NO-Alb in the treatment of acute lung injury in SCD.

transgenic sickle cell SAD mice; hypoxic lung injury; nitric oxide; nitrite