Article

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

ABSTRACT

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.

  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Asymptomatic Plasmodium infection carriers represent a major threat to malaria control worldwide as they are silent natural reservoirs and do not seek medical care. There are no standard criteria for asymptomaticPlasmodium infection; therefore, its diagnosis relies on the presence of the parasite during a specific period of symptomless infection. The antiparasitic immune response can result in reducedPlasmodium sp. load with control of disease manifestations, which leads to asymptomatic infection. Both the innate and adaptive immune responses seem to play major roles in asymptomatic Plasmodiuminfection; T regulatory cell activity (through the production of interleukin-10 and transforming growth factor-β) and B-cells (with a broad antibody response) both play prominent roles. Furthermore, molecules involved in the haem detoxification pathway (such as haptoglobin and haeme oxygenase-1) and iron metabolism (ferritin and activated c-Jun N-terminal kinase) have emerged in recent years as potential biomarkers and thus are helping to unravel the immune response underlying asymptomatic Plasmodium infection. The acquisition of large data sets and the use of robust statistical tools, including network analysis, associated with well-designed malaria studies will likely help elucidate the immune mechanisms responsible for asymptomatic infection.
    Full-text · Article · Dec 2015 · Memórias do Instituto Oswaldo Cruz
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    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
    Full-text · Article · Dec 2015 · Frontiers in Cellular Neuroscience
  • Source
    • "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 . "
    [Show abstract] [Hide abstract]
    ABSTRACT: Lack of diagnostic capacity has been a crucial barrier preventing an effective response to the challenges of malnutrition and tuberculosis (TB). Point-of-care diagnostic tests for TB in immuno-incompetent, malnourished population are thus needed to ensure rapid and accurate detection. The aim of the study was to identify potential biomarkers specific for TB infection and progression to overt disease in the malnourished population of Melghat. A prospective cohort study was conducted in the year 2009 through 2011 in six villages of the Melghat region. 275 participants consisting of malnourished cases with a) active TB (n = 32), b) latent TB infection (n = 90), c) with no clinical or bacteriological signs of active or latent TB (n = 130) and healthy control subjects (n = 23) were recruited for the study. The proteome changes of the host serum in response to Mycobacterium tuberculosis (M.tb) infection were investigated using one dimensional electrophoresis in combination with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Three most differentially expressed proteins; alpha-2-macroglobulin (A-2-M), sero-transferrin and haptoglobin were identified by MALDI-TOF MS analysis, which were up-regulated in the malnourished patients with active TB and down-regulated in the malnourished patients compared with the healthy controls. Additionally, follow-up studies indicated that the expression of these proteins increased to nearly two folds in patients who developed active disease from latent state. Our preliminary results suggest that A-2-M, sero-transferrin and haptoglobin may be clinically relevant host biomarkers for TB diagnosis and disease progression in the malnourished population. This study provides preliminary framework for
    Full-text · Article · Aug 2015 · PLoS ONE
Show more