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Prepublished online as a Blood First Edition Paper on August 29, 2002; DOI 10.1182/blood-2002-03-0979. This Article Full Text (PDF) All Versions of this Article: 2002-03-0979v1 101/2/722    most recent 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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Schwarzer, E. Articles by Arese, P. Search for Related Content PubMed PubMed Citation Articles by Schwarzer, E. Articles by Arese, P. Social Bookmarking                   What's this? Submitted April 1, 2002 Accepted August 15, 2002 Malaria-parasitized erythrocytes and hemozoin nonenzymatically generate large amounts of hydroxy-fatty acids that inhibit monocyte functions Evelin Schwarzer, Hartmut Kuehn, Elena Valente, and Paolo Arese* Institute of Biochemistry, Humboldt-University, Berlin, Germany Department of Genetics, Biology and Biochemistry, University of Torino Medical School, Turin, Italy * Corresponding author; email: paolo.arese{at}unito.it. Plasmodium falciparum digests up to 75% of RBC hemoglobin and forms hemozoin. Phagocytosed hemozoin and trophozoites inhibit important monocyte functions. Delipidized trophozoites and hemozoin were remarkably less toxic to monocytes. Parasitized RBC and hemozoin contained large amounts of mostly esterified monohydroxy derivatives (OH-PUFA), the stable end products of peroxidation of polyenoic fatty acids. The levels of OH-PUFA were (micromol/L RBC): 1.8 in nonparasitized RBC; 11.1 in rings; 35 in trophozoites; and approx. 90/L RBC equivalents in hemozoin. In parasitized RBC and hemozoin a complex mixture of monohydroxy derivatives of arachidonic (HETEs) and linoleic (HODEs) acid was determined. 13- and 9-HODE, and 9- and 12-HETE were predominant in hemozoin and parasitized RBC, respectively. The estimated concentrations of all HETE isomers were 33 and 39 micromol/L RBC or RBC equivalents in trophozoites and hemozoin, respectively. No evidence of lipoxygenase activity was found in parasitized RBC, while the large number of positional and optical isomers, the racemic structure and their generation by incubation of arachidonic acid with hemozoin indicated non-enzymatic origin via heme-catalysis. Sub/low-micromolar concentrations of 12- and 15-HETE were toxic to monocytes, while HODE isomers were ineffective. Low micromolar concentrations of HETE isomers were estimated to be similarly present in monocytes after phagocytosis of trophozoites or hemozoin. Thus, specific products of heme-catalyzed lipid peroxidation appear to contribute to hemozoin toxicity to phagocytes and may thus play a role in increased cytoadherence, vascular permeability and chemotaxis, as well as in immunodepression in malaria. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. C. Keller, C. Ouma, Y. Ouma, G. A. Awandare, G. C. Davenport, T. Were, J. B. Hittner, J. M. Vulule, J. M. Ong'echa, and D. J. Perkins Suppression of a Novel Hematopoietic Mediator in Children with Severe Malarial Anemia Infect. Immun., September 1, 2009; 77(9): 3864 - 3871. [Abstract] [Full Text] [PDF] P. Mukherjee and V. S. 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