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Infection and Immunity, August 2004, p. 4868-4873, Vol. 72, No. 8
0019-9567/04/$08.00+0 DOI: 10.1128/IAI.72.8.4868-4873.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
Elevated Nitric Oxide Production in Children with Malarial Anemia: Hemozoin-Induced Nitric Oxide Synthase Type 2 Transcripts and Nitric Oxide in Blood Mononuclear Cells
Christopher C. Keller,1 Peter G. Kremsner,2,3 James B. Hittner,4 Mary A. Misukonis,5 J. Brice Weinberg,5 and Douglas J. Perkins1*
Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania,1
Medical Research Unit, Albert Schweitzer Hospital, Lambaréné, Gabon,2
Department of Parasitology, Institute for Tropical Medicine, University of Tübingen, Tübingen, Germany,3
Department of Psychology, College of Charleston, Charleston, South Carolina,4
Department of Medicine, Durham VA and Duke University Medical Centers, Durham, North Carolina5
Received 16 February 2004/
Returned for modification 28 March 2004/
Accepted 9 April 2004
Experiments outlined here investigate the role of nitric oxide (NO) in the pathogenesis of Plasmodium falciparum-induced malarial anemia (MA). The results show that ex vivo and in vitro NO synthase (NOS) activity in peripheral blood mononuclear cells (PBMCs) is significantly elevated in children with MA and inversely associated with hemoglobin levels. Additional experiments using PBMCs from non-malaria-exposed donors demonstrate that physiologic amounts of P. falciparum-derived hemozoin augment NOS type 2 (NOS2) transcripts and NO production. Results of these experiments illustrate that elevated NO production in children with MA is associated with decreased hemoglobin concentrations and that hemozoin can induce NOS2-derived NO formation in cultured blood mononuclear cells.
* Corresponding author. Mailing address: 603 Parran Hall, 130 DeSoto St., Pittsburgh, PA 15261. Phone: (412) 624-5894. Fax: (412) 624-4953. E-mail:
djp{at}pitt.edu.
Editor: W. A. Petri, Jr.
Infection and Immunity, August 2004, p. 4868-4873, Vol. 72, No. 8
0019-9567/04/$08.00+0 DOI: 10.1128/IAI.72.8.4868-4873.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
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