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Malaria-parasitized erythrocytes and hemozoin nonenzymatically generate large amounts of hydroxy fatty acids that inhibit monocyte functions.
- Source :
-
Blood [Blood] 2003 Jan 15; Vol. 101 (2), pp. 722-8. Date of Electronic Publication: 2002 Aug 29. - Publication Year :
- 2003
-
Abstract
- Plasmodium falciparum digests up to 75% of erythrocyte (red blood cell [RBC]) hemoglobin and forms hemozoin. Phagocytosed hemozoin and trophozoites inhibit important monocyte functions. Delipidized trophozoites and hemozoin were remarkably less toxic to monocytes. Parasitized RBCs and hemozoin contained large amounts of mostly esterified monohydroxy derivatives (OH-PUFAs), the stable end products of peroxidation of polyenoic fatty acids. The concentrations of OH-PUFA were 1.8 micromoles per liter RBCs in nonparasitized RBCs, 11.1 micromoles per liter RBCs in rings, 35 micromoles per liter RBCs in trophozoites; and approximately 90 micromoles per liter RBC equivalents in hemozoin. In parasitized RBCs and hemozoin a complex mixture of monohydroxy derivatives of arachidonic (HETEs) and linoleic (HODEs) acid was determined. Respectively, 13- and 9-HODE and 9- and 12-HETE were predominant in hemozoin and parasitized RBCs. The estimated concentrations of all HETE isomers were 33 and 39 micromoles per liter RBCs or RBC equivalents in trophozoites and hemozoin, respectively. No evidence of lipoxygenase activity was found, whereas the large number of positional and optical isomers, the racemic structure, and their generation by incubation of arachidonic acid with hemozoin indicated nonenzymatic origin via heme-catalysis. Sub/low micromolar concentrations of 12- and 15-HETE were toxic to monocytes, whereas 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.
- Subjects :
- 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid pharmacology
Animals
Catalysis
Erythrocytes metabolism
Fatty Acids analysis
Hemeproteins chemistry
Hemeproteins metabolism
Humans
Hydroxy Acids analysis
Hydroxy Acids metabolism
Hydroxyeicosatetraenoic Acids pharmacology
Lipid Peroxidation
Malaria, Falciparum blood
Monocytes immunology
Monocytes metabolism
Phagocytosis
Respiratory Burst drug effects
Erythrocytes parasitology
Fatty Acids metabolism
Hemeproteins toxicity
Malaria blood
Monocytes drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0006-4971
- Volume :
- 101
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 12393662
- Full Text :
- https://doi.org/10.1182/blood-2002-03-0979