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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    • "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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    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
    PLoS ONE 08/2015; 10(8):e0133928. DOI:10.1371/journal.pone.0133928 · 3.23 Impact Factor
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    • "APPs have several antimicrobial functions, such as activating the complement cascade and opsonizing bacteria (Murphy et al., 2012). The APP haptoglobin (Hp) circulates in the blood at low concentrations that rise significantly in response to an acute infection, trauma or inflammation (Cray et al., 2009; Matson et al., 2012; Murata et al., 2004; Quaye, 2008). Nitric oxide (NO) is a multifunctional signaling molecule, which acts as a vasodilator, neurotransmitter and a modulator of inflammatory processes. "
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    ABSTRACT: Abstract Excessive deposition of metals in the environment is a well-known example of pollution worldwide. Chronic exposure of organisms to metals can have a detrimental effect on reproduction, behavior, health and survival, due to the negative effects on components of the immune system. However, little is known about the effects of chronic sublethal metal exposure on immunity, especially for wildlife. In our study, we examined the constitutive innate immunity of great tit (Parus major) nestlings (N = 234) living in four populations along a metal pollution gradient. For each nestling, we determined the individual metal concentrations (lead, cadmium, arsenic) present in the red blood cells and measured four different innate immune parameters (agglutination, lysis, haptoglobin concentrations and nitric oxide concentrations) to investigate the relationship between metal exposure and immunological condition. While we found significant differences in endogenous metal concentrations among populations with the highest concentrations closest to the pollution source, we did not observe corresponding patterns in our immune measures. However, when evaluating relationships between metal concentrations and immune parameters at the individual level, we found negative effects of lead and, to a lesser extent, arsenic and cadmium on lysis. In addition, high arsenic concentrations appear to elicit inflammation, as reflected by elevated haptoglobin concentrations. Thus despite the lack of a geographic association between pollution and immunity, this type of association was present at the individual level at a very early life stage. The high variation in metal concentrations and immune measures observed within populations indicates a high level of heterogeneity along an existing pollution gradient. Interestingly, we also found substantial within nest variation, for which the sources remain unclear, and which highlights the need of an individual-based approach.
    Science of The Total Environment 03/2015; 508:297 - 306. DOI:10.1016/j.scitotenv.2014.11.095 · 4.10 Impact Factor
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    • "In this frame, our group previously reported that Haptoglobin (Hpt), an acute-phase protein of inflammation, binds ApoE thus influencing stimulation of cholesterol esterification by the enzyme lecithin: cholesterol acyltransferase and cholesterol uptake by hepatocytes (Cigliano et al., 2009). Hpt is so far known for its role in Hemoglobin (Hb) binding and transport to the liver (Quaye, 2008), and it was initially identified as a marker of blood-brain barrier dysfunction (Chamoun et al., 2001). Further, some studies pointed out that this protein may be produced in the brain in response to different stress stimuli (Lee et al., 2002; Borsody et al., 2006; Zhao et al., 2009), and increased level of Hpt was found in cerebrospinal fluids (CSF) from patients with AD (Johnson et al., 1992), or other neurodegenerative diseases such as Parkinson' and Huntington's disease (Argüelles et al., 2010; Huang et al., 2011). "
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    ABSTRACT: Alteration in cholesterol metabolism has been implicated in the pathogenesis of several neurodegenerative disorders. Apolipoprotein E (ApoE) is the major component of brain lipoproteins supporting cholesterol transport. We previously reported that the acute-phase protein Haptoglobin (Hpt) binds ApoE, and influences its function in blood cholesterol homeostasis. Major aim of this study was to investigate whether Hpt influences the mechanisms by which cholesterol is shuttled from astrocytes to neurons. In detail it was studied Hpt effect on ApoE-dependent cholesterol efflux from astrocytes and ApoE-mediated cholesterol incorporation in neurons. We report here that Hpt impairs ApoE-mediated cholesterol uptake in human neuroblastoma cell line SH-SY5Y, and limits the toxicity of a massive concentration of cholesterol for these cells, while it does not affect cholesterol efflux from the human glioblastoma-astrocytoma cell line U-87 MG. As aging is the most important nongenetic risk factor for various neurodegenerative disorders, and our results suggest that Hpt modulates ApoE functions, we evaluated the Hpt and ApoE expression profiles in cerebral cortex and hippocampus of adolescent (2 months), adult (5 and 8 months), and middle-aged (16 months) rats. Hpt mRNA level was higher in hippocampus of 8 and 16 month-old than in 2-month old rats (p
    Frontiers in Cellular Neuroscience 08/2014; 8:212. DOI:10.3389/fncel.2014.00212 · 4.29 Impact Factor
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