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Prepublished online as a Blood First Edition Paper on July 25, 2002; DOI 10.1182/blood-2002-04-1270. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-04-1270v1 100/12/4201    most recent 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 PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Tolosano, E. Articles by Altruda, F. Search for Related Content PubMed PubMed Citation Articles by Tolosano, E. Articles by Altruda, F. Related Collections Red Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 December 2002, Vol. 100, No. 12, pp. 4201-4208 RED CELLS Enhanced splenomegaly and severe liver inflammation in haptoglobin/hemopexin double-null mice after acute hemolysis Emanuela Tolosano, Sharmila Fagoonee, Emilio Hirsch, Franklin G. Berger, Heinz Baumann, Lorenzo Silengo, and Fiorella Altruda From the Department of Genetics, Biology and Biochemistry, University of Turin and the San Giovanni Battista Hospital, Experimental Medicine Research Center, Turin, Italy; the Department of Biological Sciences, University of South Carolina, Columbia; and the Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY. Intravascular hemolysis is associated with several pathologic conditions that include hemoglobinopathies, trauma, malaria, and bacterial infections. Among plasma-protective proteins against oxidative damage caused by red blood cell rupture, haptoglobin and hemopexin are thought to play a crucial role. Haptoglobin and hemopexin, by binding with high-affinity hemoglobin and heme, respectively, exert an antioxidant action by preventing heme-catalyzed free radical production. Moreover, these proteins prevent iron loss by inhibiting glomerular filtration of hemoglobin and heme diffusion through plasma membranes. Analysis of single-null mice demonstrated the antioxidant action of haptoglobin and hemopexin in vivo and suggests that the 2 proteins cooperate in the resolution of hemolytic stress. To evaluate the physiological relevance of the haptoglobin-hemopexin system and the principal targets of its action, we generated haptoglobin-hemopexin double-knockout mice and analyzed them under basal conditions and after acute hemolysis. Whereas haptoglobin-hemopexin double-null mice displayed no obvious alteration in phenotype under basal conditions, nonlethal hemolytic stress in these animals led to pronounced splenomegaly as well as liver inflammation and fibrosis. These data demonstrate that haptoglobin and hemopexin together are essential for protection from splenomegaly and liver fibrosis resulting from intravascular hemolysis. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. B. Maniecki, H. Hasle, L. Friis-Hansen, B. Lausen, O. J. Nielsen, K. Bendix, S. K. Moestrup, and H. J. Moller Impaired CD163-mediated hemoglobin-scavenging and severe toxic symptoms in patients treated with gemtuzumab ozogamicin Blood, August 15, 2008; 112(4): 1510 - 1514. [Abstract] [Full Text] [PDF] V. Chandra, A. Kar-Roy, S. Kumari, S. Mayor, and S. 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