Haptoglobin, inflammation and disease

Department of Medical Biochemistry, University of Ghana Medical School, Korle-Bu-Accra, Ghana.
Transactions of the Royal Society of Tropical Medicine and Hygiene (Impact Factor: 1.84). 09/2008; 102(8):735-42. DOI: 10.1016/j.trstmh.2008.04.010
Source: PubMed


Haptoglobin is an acute phase protein that scavenges haemoglobin in the event of intravascular or extravascular haemolysis. The protein exists in humans as three main phenotypes, Hp1-1, Hp2-2 and Hp2-1. Accumulated data on the protein's function has established its strong association with diseases that have inflammatory causes. These include parasitic (malaria), infectious (HIV, tuberculosis) and non-infectious diseases (diabetes, cardiovascular disease and obesity) among others. Phenotype-dependent poor disease outcomes have been linked with the Hp2-2 phenotype. The present review brings this association into perspective by looking at the functions of the protein and how defects in these functions associated with the Hp2 allele affect disease outcome. A model is provided to explain the mechanism, which appears to be largely immunomodulatory.

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    • "infection, it is scavenged by haptoglobin (Hp) and prevents the release of haem. The complex Hp-Hb is recognised by CD163 on the macrophage and hepatocyte surfaces in the spleen and liver, respectively (Philippidis et al. 2004, Quaye 2008). Free haem can also be scavenged by haemopexin, albumin, α1-microglobulin, and high and low-density lipoproteins (Bunn & Jandl 1966, Miller & Shaklai 1999, Paoli et al. 1999, Allhorn et al. 2002, Fasano et al. 2007, Tolosano et al. 2010). "
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    • "This brain region, crucial for learning and memory, is considered one of the most vulnerable sites in early AD and other neurodegenerative diseases development (Gómez-Isla et al., 1996; Price et al., 2001), and is particularly susceptible to disruption by dietary factors. In addition, in view of the previously described Hpt antioxidant function (Salvatore et al., 2007, 2009; Quaye, 2008), we also investigated whether diet-dependent Hpt changes are associated with inflammation and with changes in the level of nitro-tyrosine (N-Tyr), here selected as marker of the extent of protein oxidative modification. "
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    ABSTRACT: Obesity and dietary fats are well known risk factors for the pathogenesis of neurodegenerative diseases. The analysis of specific markers, whose brain level can be affected by diet, might contribute to unveil the intersection between inflammation/obesity and neurodegeneration. Haptoglobin (Hpt) is an acute phase protein, which acts as antioxidant by binding free Haemoglobin (Hb), thus neutralizing its pro-oxidative action. We previously demonstrated that Hpt plays critical functions in brain, modulating cholesterol trafficking in neuroblastoma cell lines, beta-amyloid (Aβ) uptake by astrocyte, and limiting Aβ toxicity on these cells. A major aim of this study was to evaluate whether a long term (12 or 24 weeks) high-fat diet (HFD) influences Hpt and Hb expression in rat hippocampus. We also assessed the development of obesity-induced inflammation by measuring hippocampal level of TNF-alpha, and the extent of protein oxidation by titrating nitro-tyrosine (N-Tyr). Hpt concentration was lower (p
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    • "Levels of haptoglobin are reduced in newly diagnosed PTB patients . John FM et al , 1998 ; Quaye IK et al , 2008 ; Adedapo KS et al , 2009 Table enlists the roles of the three identified proteins in malnutrition and tuberculosis reported in various studies . "
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