scholarly journals A critical role for the host mediator macrophage migration inhibitory factor in the pathogenesis of malarial anemia

2006 ◽  
Vol 203 (5) ◽  
pp. 1185-1196 ◽  
Author(s):  
Michael A. McDevitt ◽  
Jianlin Xie ◽  
Shanmugasundaram Ganapathy-Kanniappan ◽  
Jason Griffith ◽  
Aihua Liu ◽  
...  
Keyword(s):  
Migration Inhibitory Factor ◽  
Malaria Infection ◽  
Macrophage Migration Inhibitory Factor ◽  
Mononuclear Cells ◽  
Critical Role ◽  
Inhibitory Factor ◽  
Mitogen Activated Protein Kinase ◽  
Macrophage Migration ◽  
Erythroid Progenitor ◽  
Malarial Anemia

The pathogenesis of malarial anemia is multifactorial, and the mechanisms responsible for its high mortality are poorly understood. Studies indicate that host mediators produced during malaria infection may suppress erythroid progenitor development (Miller, K.L., J.C. Schooley, K.L. Smith, B. Kullgren, L.J. Mahlmann, and P.H. Silverman. 1989. Exp. Hematol. 17:379–385; Yap, G.S., and M.M. Stevenson. 1991. Ann. NY Acad. Sci. 628:279–281). We describe an intrinsic role for macrophage migration inhibitory factor (MIF) in the development of the anemic complications and bone marrow suppression that are associated with malaria infection. At concentrations found in the circulation of malaria-infected patients, MIF suppressed erythropoietin-dependent erythroid colony formation. MIF synergized with tumor necrosis factor and γ interferon, which are known antagonists of hematopoiesis, even when these cytokines were present in subinhibitory concentrations. MIF inhibited erythroid differentiation and hemoglobin production, and it antagonized the pattern of mitogen-activated protein kinase phosphorylation that normally occurs during erythroid progenitor differentiation. Infection of MIF knockout mice with Plasmodium chabaudi resulted in less severe anemia, improved erythroid progenitor development, and increased survival compared with wild-type controls. We also found that human mononuclear cells carrying highly expressed MIF alleles produced more MIF when stimulated with the malarial product hemozoin compared with cells carrying low expression MIF alleles. These data suggest that polymorphisms at the MIF locus may influence the levels of MIF produced in the innate response to malaria infection and the likelihood of anemic complications.

scholarly journals A critical role for the host mediator macrophage migration inhibitory factor in the pathogenesis of malarial anemia

2015 ◽  
Vol 212 (5) ◽  
pp. 825-825
Author(s):  
Michael A. McDevitt ◽  
Jianlin Xie ◽  
Shanmugasundaram Ganapathy-Kanniappan ◽  
Jason Griffith ◽  
Aihua Liu ◽  
...  
Keyword(s):  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Critical Role ◽  
Inhibitory Factor ◽  
Macrophage Migration ◽  
Malarial Anemia

scholarly journals Role of Monocyte-Acquired Hemozoin in Suppression of Macrophage Migration Inhibitory Factor in Children with Severe Malarial Anemia

2006 ◽  
Vol 75 (1) ◽  
pp. 201-210 ◽  
Author(s):  
Gordon A. Awandare ◽  
Yamo Ouma ◽  
Collins Ouma ◽  
Tom Were ◽  
Richard Otieno ◽  
...  
Keyword(s):  
Migration Inhibitory Factor ◽  
Peripheral Blood ◽  
Macrophage Migration Inhibitory Factor ◽  
Inflammatory Responses ◽  
Sub Saharan Africa ◽  
Inhibitory Factor ◽  
Macrophage Migration ◽  
Severe Malarial Anemia ◽  
Malarial Anemia

ABSTRACT Severe malarial anemia (SMA), caused by Plasmodium falciparum infections, is one of the leading causes of childhood mortality in sub-Saharan Africa. Although the molecular determinants of SMA are largely undefined, dysregulation in host-derived inflammatory mediators influences disease severity. Macrophage migration inhibitory factor (MIF) is an important regulator of innate inflammatory responses that has recently been shown to suppress erythropoiesis and promote pathogenesis of SMA in murine models. To examine the role of MIF in the development of childhood SMA, peripheral blood MIF production was examined in Kenyan children (aged <3 years, n = 357) with P. falciparum malarial anemia. All children in the study were free from bacteremia and human immunodeficiency virus type 1. Since deposition of malarial pigment (hemozoin [Hz]) contributes to suppression of erythropoiesis, the relationship between MIF concentrations and monocytic acquisition of Hz was also examined in vivo and in vitro. Circulating MIF concentrations declined with increasing severity of anemia and significantly correlated with peripheral blood leukocyte MIF transcripts. However, MIF concentrations in peripheral blood were not significantly associated with reticulocyte production. Multivariate regression analyses, controlling for age, gender, and parasitemia, further revealed that elevated levels of pigment-containing monocytes (PCM) was associated with SMA and decreased MIF production. In addition, PCM levels were a better predictor of hemoglobin and MIF concentrations than parasite density. Additional experiments in malaria-naive individuals demonstrated that hemozoin caused both increased and decreased MIF production in cultured peripheral blood mononuclear cells (PBMC) in a donor-specific manner, independent of apoptosis. However, PBMC MIF production in children with acute malaria progressively declined with increasing anemia severity. Results presented here demonstrate that acquisition of hemozoin by monocytes is associated with suppression of peripheral blood MIF production and enhanced severity of anemia in childhood malaria.

scholarly journals MIF(Macrophage Migration Inhibitory Factor) Promoter Polymorphisms and Susceptibility to Severe Malarial Anemia

2009 ◽  
Vol 200 (4) ◽  
pp. 629-637 ◽  
Author(s):  
Gordon A. Awandare ◽  
Jeremy J. Martinson ◽  
Tom Were ◽  
Collins Ouma ◽  
Gregory C. Davenport ◽  
...  
Keyword(s):  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Inhibitory Factor ◽  
Macrophage Migration ◽  
Promoter Polymorphisms ◽  
Severe Malarial Anemia ◽  
Malarial Anemia

scholarly journals Macrophage Migration Inhibitory Factor Release by Macrophages after Ingestion of Plasmodium chabaudi-Infected Erythrocytes: Possible Role in the Pathogenesis of Malarial Anemia

2000 ◽  
Vol 68 (4) ◽  
pp. 2259-2267 ◽  
Author(s):  
James A. Martiney ◽  
Barbara Sherry ◽  
Christine N. Metz ◽  
Marisol Espinoza ◽  
Angel S. Ferrer ◽  
...  
Keyword(s):  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Inhibitory Factor ◽  
Interleukin 12 ◽  
Macrophage Migration ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Erythropoiesis Inhibitor ◽  
Necrosis Factor ◽  
Malarial Anemia

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-1β, tumor necrosis factor alpha, and gamma interferon while injection of interleukin-12 protects susceptible mice against lethal P. chabaudiinfection. 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.

scholarly journals Macrophage Migration Inhibitory Factor: Critical Role in Obesity, Insulin Resistance, and Associated Comorbidities

2010 ◽  
Vol 2010 ◽  
pp. 1-7 ◽  
Author(s):  
Robert Kleemann ◽  
Richard Bucala
Keyword(s):  
Insulin Resistance ◽  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Current Knowledge ◽  
Critical Role ◽  
Inhibitory Factor ◽  
Low Grade ◽  
Macrophage Migration ◽  
Animal Models Of Disease ◽  
Models Of Disease

Obesity is associated with insulin resistance, disturbed glucose homeostasis, low grade inflammation, and comorbidities such as type 2 diabetes and cardiovascular disease. The cytokine macrophage migration inhibitory factor (MIF) is an ubiquitously expressed protein that plays a crucial role in many inflammatory and autoimmune disorders. Increasing evidence suggests that MIF also controls metabolic and inflammatory processes underlying the development of metabolic pathologies associated with obesity. This is a comprehensive summary of our current knowledge on the role of MIF in obesity and obesity-associated comorbidities, based on human clinical data as well as animal models of disease.

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