Identification of hydroxyeicosatetraenoic acid components of schistosomal hemozoin.
During the late stages of Schistosoma mansoni infection, adult schistosomes catabolize host erythrocytic hemoglobin. In order to evade the toxic effects of free heme, the blood fluke biomineralizes dimeric heme into an inert crystalline pigment called hemozoin. In the present study, the chemical reactivity of schistosomal hemozoin (SmHz) toward lipid oxidation was examined, and the biological consequences of reactivity were investigated. Mass spectrometric analysis of polar lipid content associated with SmHz identified a variety of primary and secondary polyunsaturated fatty acid oxidation products, including hydroxyeicosatetraenoic acids. Furthermore, RAW 264.7 macrophage-like cells challenged with lipopolysaccharide prior to phagocytosis of SmHz experienced a decrease in nitric oxide production as compared to control experiments. The presence of these biologically active oxidation products suggests native SmHz is capable of modulating the innate immune response and may play a potential role in the pathogenesis of schistosomiasis.
Carter
Melissa D
MD
Vanderbilt University, Department of Chemistry, Station B 351822, Nashville, TN 37235, USA.
Reese Harry
S
S
Wright
David W
DW
D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005260:Female; D006420:Hemeproteins / Q000737:chemistry* / Q000494:pharmacology / Q000648:ultrastructure; D006893:Hydroxyeicosatetraenoic Acids / Q000032:analysis* / Q000737:chemistry / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008855:Microscopy, Electron, Scanning; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D012550:Schistosoma mansoni / Q000737:chemistry* / Q000302:isolation & purification; D012552:Schistosomiasis / Q000469:parasitology
D006420:Hemeproteins; D006893:Hydroxyeicosatetraenoic Acids; D008070:Lipopolysaccharides; C020753:hemozoin; D052247:Nitric Oxide Synthase Type II