Macrophage migration inhibitory factor release by macrophages after ingestion of Plasmodium chabaudi-infected erythrocytes: possible role in the pathogenesis of malarial anemia

Details

Serval ID
serval:BIB_7A81D2F78F56
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Macrophage migration inhibitory factor release by macrophages after ingestion of Plasmodium chabaudi-infected erythrocytes: possible role in the pathogenesis of malarial anemia
Journal
Infection and Immunity
Author(s)
Martiney  J. A., Sherry  B., Metz  C. N., Espinoza  M., Ferrer  A. S., Calandra  T., Broxmeyer  H. E., Bucala  R.
ISSN
0019-9567 (Print)
Publication state
Published
Issued date
04/2000
Volume
68
Number
4
Pages
2259-67
Notes
Journal Article
Research Support, U.S. Gov't, P.H.S. --- Old month value: Apr
Abstract
Human falciparum malaria, caused by Plasmodium falciparum infection, results in 1 to 2 million deaths per year, mostly children under the age of 5 years. The two main causes of death are severe anemia and cerebral malaria. Malarial anemia is characterized by parasite red blood cell (RBC) destruction and suppression of erythropoiesis (the mechanism of which is unknown) in the presence of a robust host erythropoietin response. The production of a host-derived erythropoiesis inhibitor in response to parasite products has been implicated in the pathogenesis of malarial anemia. The identity of this putative host factor is unknown, but antibody neutralization studies have ruled out interleukin-1beta, tumor necrosis factor alpha, and gamma interferon while injection of interleukin-12 protects susceptible mice against lethal P. chabaudi infection. In this study, we report that ingestion of P. chabaudi-infected erythrocytes or malarial pigment (hemozoin) induces the release of macrophage migration inhibitory factor (MIF) from macrophages. MIF, a proinflammatory mediator and counter-regulator of glucocorticoid action, inhibits erythroid (BFU-E), multipotential (CFU-GEMM), and granulocyte-macrophage (CFU-GM) progenitor-derived colony formation. MIF was detected in the sera of P. chabaudi-infected BALB/c mice, and circulating levels correlated with disease severity. Liver MIF immunoreactivity increased concomitant with extensive pigment and parasitized RBC deposition. Finally, MIF was elevated three- to fourfold in the spleen and bone marrow of P. chabaudi-infected mice with active disease, as compared to early disease, or of uninfected controls. In summary, the present results suggest that MIF may be a host-derived factor involved in the pathophysiology of malaria anemia.
Keywords
Anemia/etiology/*parasitology Animals Bone Marrow/metabolism/parasitology Cells, Cultured Dose-Response Relationship, Drug Enzyme-Linked Immunosorbent Assay Erythrocytes/*parasitology Erythroid Progenitor Cells/metabolism Erythropoiesis/drug effects/physiology Erythropoietin/pharmacology Female Immunohistochemistry Leukopoiesis Liver/metabolism/parasitology Macrophage Migration-Inhibitory Factors/*biosynthesis/blood/physiology Macrophages/*metabolism Malaria/complications/*parasitology Mice Mice, Inbred BALB C Mice, Inbred C3H Plasmodium chabaudi/*immunology Spleen/metabolism/parasitology Time Factors
Pubmed
Web of science
Open Access
Yes
Create date
25/01/2008 13:28
Last modification date
20/08/2019 14:36
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