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Blood First Edition Paper, prepublished online November 4, 2009; DOI 10.1182/blood-2009-04-216408. This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted 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 CrossRef Google Scholar Articles by Dimitrov, J. D Articles by Lacroix-Desmazes, S. PubMed PubMed Citation Articles by Dimitrov, J. D Articles by Lacroix-Desmazes, S. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 13, 2009; accepted October 11, 2009. Induction of heme oxygenase-1 in factor VIII-deficient mice reduces the immune response to therapeutic factor VIII Jordan D Dimitrov1, Suryasarathi Dasgupta2, Ana-Maria Navarrete3, Sandrine Delignat1, Yohann Repesse1, Yann Meslier1, Cyril Planchais1, Maud Teyssandier1, Roberto Motterlini4, Jagadeesh Bayry1, Srinivas V Kaveri1 and Sebastien Lacroix-Desmazes1,5 1 INSERM, UMR S 872, Paris, France; 2 Universite Pierre et Marie Curie-Paris6, UMR S 872, Paris, France; 3 Universite Paris Descartes, UMR S 872, Paris, France; 4 Department of Drug Discovery and Development, Italian Institute of Technology, Genova, Italy * Corresponding author; email: sebastien.lacroix-desmazes{at}crc.jussieu.fr Abstract Replacement therapy with exogenous factor VIII (FVIII) to treat hemorrhages induces anti-FVIII inhibitory IgG in up to 30% of patients with hemophilia A. Chronic inflammation associated with recurrent bleedings is a proposed risk factor for FVIII inhibitor development. Heme oxygenase-1 (HO-1) is a stress-inducible enzyme with potent anti-inflammatory activity. Here, we demonstrate that induction of HO-1 prior to FVIII administration drastically reduces the onset of the anti-FVIII humoral immune response. The protective effect was specific for HO-1 since it was reproduced upon administration of the end products of HO-1 activity, carbon monoxide (CO) and bilirubin, and prevented by the pharmacological inhibition of HO-1 using tin mesoporphyrin IX. HO-1 induction was associated with decreased MHC class II expression by splenic antigen-presenting cells and reduced T-cell proliferation. Triggering the endogenous anti-inflammatory machinery before FVIII administration may represent a novel therapeutic option for preventing the development of FVIII inhibitors in hemophilia A patients. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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