title: Leukocyte activation by malarial pigment.
abstract: Malarial pigment, a unique hemozoin crystal composed of unit cells of heme dimers, is present in large amounts in circulating monocytes and neutrophils and can persist unchanged in macrophages for several months. In the present study, we investigated the effect of hemozoin not only on macrophages, but also on neutrophils. We used beta-hematin (BH), a chemically synthetic crystal structurally identical to hemozoin, for these studies. In vitro, BH up-regulated the expression of tumor necrosis factor-alpha in whole blood and in isolated peritoneal macrophages, indicating that hemozoin is able to stimulate monocytes. BH stimulated murine peritoneal neutrophils to express macrophage inflammatory protein-2 (MIP-2), a homologue of human interleukin-8 that is used as a marker of neutrophil activation. Injecting BH into the peritoneal cavity resulted in a dose-dependent migration of neutrophils and a high level of myeloperoxidase activity of peritoneal cells. Finally, BH directly induced neutrophil chemotaxis in vitro. Taken together, these results suggest that the malarial pigment hemozoin can activate leukocytes and may participate in the pathology of severe malaria.
authors.affiliation: Department of Applied Biology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan.
authors.forename: Nguyen Tien
authors.initials: NT
authors.lastname: Huy
authors.forename: Dai Thi Xuan
authors.initials: DT
authors.lastname: Trang
authors.forename: Tohru
authors.initials: T
authors.lastname: Kariu
authors.forename: Motohiro
authors.initials: M
authors.lastname: Sasai
authors.forename: Katsuya
authors.initials: K
authors.lastname: Saida
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Harada
authors.forename: Kaeko
authors.initials: K
authors.lastname: Kamei
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D054426:Chemokine CXCL2; D018925:Chemokines / Q000096:biosynthesis; D002633:Chemotaxis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006420:Hemeproteins / Q000138:chemical synthesis / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000502:physiology; D008288:Malaria / Q000469:parasitology; D008297:Male; D051379:Mice; D023421:Models, Animal; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D010529:Peritoneal Cavity; D012333:RNA, Messenger / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013047:Specific Pathogen-Free Organisms; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation
chemical_list: D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D006420:Hemeproteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C020753:hemozoin