The basis of the immunomodulatory activity of malaria pigment (hemozoin)
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- 作者：Clare K. Carney ; Alexandra C. Schrimpe ; Kristin Halfpenny ; Reese S. Harry ; Crystal M. Miller ; Malgorzata Broncel ; Sarah L. Sewell ; Jacob E. Schaff ; Ravinder Deol and Melissa D. Carter ; et al.
- 关键词：Hemozoin ; β ; Hematin ; Malaria ; Lipid peroxidation ; Immunomodulation
- 刊名：Journal of Biological Inorganic Chemistry
- 出版年：2006
- 出版时间：October, 2006
- 年：2006
- 卷：11
- 期：7
- 页码：917-929
- 全文大小：301 KB
- 刊物类别：Biomedical and Life Sciences
- 刊物主题：Life Sciences
Biochemistry
Microbiology - 出版者：Springer Berlin / Heidelberg
- ISSN：1432-1327
文摘
The most common and deadly form of the malaria parasite, Plasmodium falciparum, is responsible for 1.5–2.7 million deaths and 300–500 million acute illnesses annually [Bremen in J. Trop. Med. Hyg. 64:1–11 (2001); World Health Organization (2002)]. Hemozoin, the biomineral formed to detoxify the free heme produced during parasitic hemoglobin catabolism, has long been suspected of contributing to the pathological immunodeficiencies that occur during malarial infection. While there is a growing consensus in the literature that native hemozoin maintains immunosuppressive activity, there is considerable controversy over the reactivity of the synthetic form, β-hematin (BH). Given the emerging importance of hemozoin in modulating a host immune response to malarial infection, a careful examination of the effects of the constitutive components of the malaria pigment on macrophage response has been made in order to clarify the understanding of this process. Herein, we present evidence that BH alone is unable to inhibit stimulation of NADPH oxidase and inducible nitric oxide synthase, the key enzymes involved in oxidative burst, and is sensitive to the microbicidal agents of these enzymes both in vitro and in vivo. Further, by systematically examining each of the malaria pigment’s components, we were able to dissect their impact on the immune reactivity of a macrophage model cell line. Reactions between BH and red blood cell (RBC) ghosts effectively reconstituted the observed immunomodulatory reactivity of native hemozoin. Together, these results suggest that the interaction between hemozoin and the RBC lipids results in the generation of toxic products and that these products are responsible for disrupting macrophage function in vivo.