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PubMed2001

Haptoglobin and CD163: captor and receptor gating hemoglobin to macrophage lysosomes.

The plasma protein haptoglobin and the endocytic hemoglobin receptor HbSR/CD163 are key molecules in the process of removing hemoglobin released from ruptured erythrocytes. Hemoglobin in plasma is instantly bound with high affinity to haptoglobin--an interaction leading to the recognition of the complex by HbSR/CD163 and endocytosis in macrophages. The haptoglobin-dependent HbSR/CD163 scavenging system for hemoglobin clearance prevents toxic effects of hemoglobin in plasma and kidney and explains the decrease in the haptoglobin plasma concentration in patients with accelerated hemolysis. The HbSR/CD163 activity may be of quantitative importance for iron uptake in macrophages in general and for some iron-associated pathological processes, e.g. the atherogenesis-promoting oxidation of LDL leading to foam cell formation and apoptosis in the vessel wall.

Animals↗
PubMed1980

Inhibition of prostaglandin synthesizing enzymes by haptoglobin and plasma of rats with inflammation.

Administration of carrageenin or adjuvant to rats to induce inflammation produced increases in the plasma haptoglobin level. Simultaneously, there was an increase in the activity of the plasma inhibitor of prostaglandin E2 synthesis. Partially purified haptoglobin inhibited the microsomal over-all conversion of arachidonic acid to prostaglandin E2. The addition of the haptoglobin inhibited two heme-dependent reactions catalyzed by a purified enzyme of seminal vesicle microsome, i.e., the prostaglandin G2 synthesis from arachidonic acid and the conversion of prostaglandin G2 to H2. However, the plasma inhibitory activity was accounted for only partially by the haptoglobin contained in the plasma from treated rats.

Animals↗
PubMed1993

Induction of serum haptoglobin by administration of ethionine to cows.

In order to assess the association of cow serum haptoglobin with fatty liver, haptoglobin concentrations were evaluated by single radial immunodiffusion in sera from cows after administration of ethionine (an analogue of methionine). Haptoglobin concentrations were found to be increased in the sera of the ethionine-administered cows. This result suggests that the induction of haptoglobin is associated in the pathogenesis of fatty liver.

Animals↗
PubMed2002

Study of chaperone-like activity of human haptoglobin: conformational changes under heat shock conditions and localization of interaction sites.

With respect to the mechanism of chaperone-like activity, we examined the behavior of haptoglobin under heat shock conditions. Secondary structure changes during heat treatment were followed by circular dichroism, Raman and infrared spectroscopy. A model of the haptoglobin tetramer, based on its sequence homology with serine proteases and the CCP modules, has been proposed. Sequence regions responsible for the chaperone-like activity were not fully identical with the region that takes part in formation of the hemoglobin-haptoglobin complex. We can postulate the presence of at least two different chaperone-binding sites on each haptoglobin heavy chain.

Amino Acid Sequence↗
PubMed1976

Turbidimetric determination of haptoglobin.

A specific, accurate and simple determination of haptoglobin is described with an antiserum against the antigenic determinants of the three haptoglobin phenotypes 1-1, 2-1 and 2-2. Antihaptoglobin is the determining factor in the formation of an antigen-antibody complex with maximal light absorption properties. Haptoglobin concentration is expressed as hemoglobin binding capacity. For the three haptoglobin phenotypes we found similar correlation between the turbidimetric method and the direct measurement of hemoglobin binding capacity by agar-electrophoresis.

Electrophoresis, Agar Gel↗
PubMed2004

Haptoglobin concentrations in blood and milk after endotoxin challenge and quantification of mammary Hp mRNA expression.

Haptoglobin (Hp), an acute phase protein mostly secreted by the liver, is an inflammatory marker. To use the full diagnostic potential of Hp measurements for mastitis, we developed and validated an ELISA sensitive to quantify even basal and subclinical concentrations in both blood and milk. Bovine Hp was purified from serum and was used as a standard and to generate polyclonal antiserum. The limit of detection was 0.07 microg of Hp/mL. From 6 cows challenged by intracisternal injection of lipopolysaccharide (LPS) into one quarter, blood samples were collected 0, 3, 6, 9, and 12 h after LPS administration. Milk samples from the treated and from the contralateral quarters were collected 0, 3, 6, 9, 12, 24, 36, 48, and 60 h after LPS administration. Haptoglobin concentrations in blood were increased above basal at 9 h, whereas milk Hp concentration increased 3 h after LPS administration. We therefore evaluated Hp mRNA synthesis within the mammary gland and specifically demonstrated Hp mRNA expression in parenchymal tissue, in tissue around the cisternal milk ducts and also in teat tissue by RT-PCR. Haptoglobin mRNA expression was then quantitatively evaluated by real-time RT-PCR in mammary biopsies collected from the treated and the control quarter before, and 3, 6, 9, and 12 h after LPS challenge from 6 other cows. Haptoglobin mRNA expression in the treated vs. the control quarters was different. The relation between mammary Hp expression and milk Hp concentrations needs further investigation, but the results suggest good diagnostic potential of this parameter for mastitis.

Animals↗
PubMed2006

Haptoglobin 2-2 phenotype is a risk factor for type 2 diabetes in Ghana.

We have investigated the role of haptoglobin gene polymorphisms in 129 type 2 diabetic patients and 87 non-diabetic subjects, classified by the ADA criteria, in Ghana. The diabetic subjects were recruited consecutively from the National Diabetic Management and Research Center of the University of Ghana Medical School, Korle-Bu, Accra, Ghana and were categorized by their haptoglobin phenotypes. The haptoglobin 2 allele was determined to be a risk factor for type 2 diabetes in Ghana (OR = 6.1, 95% CI = 1.8-21.2; P = .0.001) while the Hp1 allele appeared protective (OR = 0.56, 95% CI = 0.31-1.0; P = .06). The deleterious role of the Hp2 allele was further evidenced by the reduced risk associated with Hp2-1M mutant heterozygotes, who produce less Hp2 protein than the normal Hp2-1 heterozygote. (OR = 0.52, 95% CI = 0.27-1.0; P = 0.06). The subjects with the homozygous Hp2 allele were also hypertensive and overweight. There was no difference (p > 0.05) in the levels of triglycerides, total cholesterol, LDL and HDL between diabetic subjects with different haptoglobin phenotypes. We conclude that hypertensive and overweight individuals with the Hp2-2 phenotype in Ghana are at a high risk of developing type 2 diabetes and may require a more aggressive management.

Adult↗
PubMedDate not supplied

Quantitative determination of haptoglobin (HAP) in human and bovine sera by capillary zone electrophoresis (CZE).

This study describes an original assay for serum haptoglobin determination by measuring the capacity of human haptoglobin (hHAP) and bovine haptoglobin (bHAP) to bind haemoglobin (Hb) as established by capillary zone electrophoresis (CZE). This method involves the addition of Hb in excess to the serum and the separation of the HAP-Hb complexes from free haemoglobin by CZE. Protein migration was recorded at a wavelength of 415 nm which reveals Hb alone (free or bound), and the concentration of HAP was indirectly estimated by measuring bound Hb. Different CZE conditions and the peak migration time of Hb from various species (human, equine, bovine, canine) were investigated. The electrophoretic separation of free human Hb (hHb) in excess and the hHAP-hHb complex was fully achieved by CZE, allowing a quantitative determination of hHAP. However, bovine haemoglobin (bHb) bound to bHAP and free bHb were poorly separated under the same conditions. The best detachment between bHAP-Hb complexes and free Hb was only attained in the bovine sample by use of canine haemoglobin (cHb). CZE assays performed with cHb gave very close values to those of a classic photometric method which measured the peroxidase activity of the haptoglobin-cyanmethaemoglobin complexes (y = 1.0168x - 0.072; r2 = 0.97). CZE assay was fast (< 10 min), inexpensive, did not require the use of a specific antibody and was reproducible (coefficient of variation, CV 3.6%).

Animals↗
PubMed2000

Haptoglobin polymorphism and mortality in patients with tuberculosis.

SETTING: A rural Zimbabwean hospital and the surrounding community. OBJECTIVES: To determine whether a particular haptoglobin phenotype is associated with increased susceptibility to clinical pulmonary tuberculosis, and to determine the outcome of treatment for pulmonary tuberculosis according to haptoglobin phenotype. DESIGN: A case-control study, and a prospective cohort study. RESULTS: We studied 98 consecutive patients with sputum-positive pulmonary tuberculosis and 98 sex- and age-matched controls. The haptoglobin (Hp) phenotype distributions did not differ significantly between the tuberculosis patients and controls (P = 0.5). During the 18-month follow-up period after the start of tuberculosis treatment, 6/18 (33%) cases with Hp 2-2 phenotype died compared to 9/47 (19%) with Hp 2-1 and 3/31 (10%) with Hp 1-1. In a logistic regression model, the odds of dying were 6.1-fold greater with Hp 2-2 than with Hp 1-1 (95%CI 1.04-35.1, P = 0.04). CONCLUSION: Our results suggest that there is equal susceptibility to clinical pulmonary tuberculosis disease amongst different haptoglobin phenotypes. Nonetheless, tuberculosis patients with Hp 2-2 phenotype had a higher risk of mortality.

Adult↗
PubMed1975

Changes in haptoglobin and other plasma proteins of rats during exposure to pure oxygen at 760 torr.

Changes in plasma haptoglobin, total protein, hematocrit, and hemoglobin content of blood were studied in rats at various times during a 7-d exposure to oxygen at 760 torr. Plasma haptoglobin and other plasma proteins were fractionated and quantitatively evaluated for a 3-d exposure period. Total protein and haptoglobin were depressed after 7 d of exposure. Significant changes were not noted before this time. With a 3-d exposure, for which plasma proteins were fractionated, fibrinogen showed a considerable increase whereas albumin, gamma globulins, and the beta 1 globulin fraction decreased significantly. Individual variations in albumin and haptoglobin were correlated inversely to the hematocrit. These variations indicate that the altered composition of the plasma protein is due, in part, to a variable loss of the various plasma protein fractions as a result of increased vascular permeability.

Aerospace Medicine↗
PubMed1979

Evaluation of a nephelometric assay for haptoglobin and its clinical usefulness.

Serum haptoglobin has been advocated as an indicator of intravascular hemolysis. We have evaluated a nephelometric determination of serum haptoglobin. The assay is sensitive and exhibits within-run precision in the range of 2.5-7.4% coefficient of variation (CV) and between-run precision of 7.0% (CV). In addition, when haptoglobin values determined with the nephelometric assay were compared with hemoglobin-binding capacity determined by electrophoresis, the correlation coefficient was 0.968. The assay is essentially independent of phenotype and free of significant interference by hemolysis. The clinical correlation of haptoglobin values obtained for 100 selected patients with the nephelometric technique correlated well, if less than 250 mg/L, with the presence of hemolytic disease.

Anemia, Hemolytic↗
PubMed2002

[Genetic variants of haptoglobin in patients with nephrotuberculosis].

Clinical, X-ray, ultrasound, and laboratory studies were made in 152 patients with nephrotic tuberculosis. Haptoglobin phenotypes were defined in the examinees. Nephorotic tuberculosis was found to occur in patients with haptoglobin 2-2 most commonly. There was a relationship between the carriage of a genetically determined haptoglobin phenotype and a difference in the clinical manifestations of hephrotic tuberculosis. The patients with haptoglobin 2-2 were seen to have more severe hephrotic tuberculosis.

Adolescent↗
PubMed1976

[Hereditary polymorphism in the haptoglobin system of schizophrenic patients and healthy subjects].

Hereditary polymorphism of haptoglobin is studied by means of starch gel electrophoresis in schizophrenic patients (200 persons) and in healthy people (154 persons), in habitants of Minsk. It is concluded that Minsk inhabitants do not differ considerably from the rest European population in their frequencies of haptoglobin alleles. No reliable differences in the distribution of haptoglobin genotypes were found between patients and healthy persons. However, hereditary types of haptoglobins turned to be markers of the course and the prognosis of schizophrenia.

Gene Frequency↗
PubMed1992

[The significance of haptoglobin in the differential diagnosis of tuberculosis of the female genital organs].

Study included 115 women with suspicion of genital tuberculosis. Combined clinical, X-ray and laboratory examination made it possible to classify patients into 3 groups: group 1 included 44 patients with active genital tuberculosis, group 2 32 women with clinically cured tuberculosis of internal genitalia and group 3 39 women with nonspecific genital diseases. The haptoglobin-tuberculin test was given to all patients. High haptoglobin parameters before or 72 h after tuberculin administration were found only in the group of patients with active genital tuberculosis. In groups 2 and 3 the haptoglobin level did not exceed normal values both before and after tuberculin administration in a dose of 50 TU. The informative value of serum haptoglobin parameters in patients with active tuberculosis of internal genitalia constituted 88.6%.

Adult↗
PubMedDate not supplied

Haptoglobin alpha-subunit and hepatocyte growth factor can potentially serve as serum tumor biomarkers in small cell lung cancer.

BACKGROUND: Small cell lung cancer (SCLC) frequently presents as metastatic disease. It would be useful to detect serum tumor biomarkers at an earlier stage in order to improve the overall survival. MATERIALS AND METHODS: Serum samples from SCLC patients (6 limited disease, 7 extensive disease, 4 relapsed disease, 4 no evidence of disease post-treatment) and 5 normal controls were used to identify tumor biomarkers utilizing proteomics. Serum hepatocyte growth factor was also studied using standard ELISA. RESULTS: Utilizing MALDI-TOF-Mass Spectrometry (MS) based protein identification techniques, a SCLC specific overexpressed protein was identified to be haptoglobin alpha-subunit, with its serum level correlating with the disease stage. The mean level of alpha-haptoglobin was increased in SCLC serum as compared to the normal controls. Serum HGF was also studied as potential tumor biomarker and was found to correlate with the disease status. Either serum alpha-haptoglobin relative level (above 1.9 U), or HGF level (above 500 pg/ml) was associated with a trend towards worse survival. CONCLUSION: Our current findings suggest that serum levels of alpha-haptoglobin and HGF may serve as useful serum tumor biomarkers in SCLC. It would now also be useful to determine if these serum biomarkers are altered in response to therapy for this disease.

Biomarkers, Tumor↗
PubMedDate not supplied

Administration of haptoglobin during cardiopulmonary bypass surgery.

A study was undertaken to evaluate hemolysis and subsequent renal damage in 14 patients undergoing cardiopulmonary bypass (CPB) surgery. In all patients, free haptoglobin disappeared completely 30 to 90 minutes into CPB, while free hemoglobin (Hb) levels increased progressively. The NAG index and alpha 1M index also increased progressively, indicating renal tubular injury due to hemolysis (Study 1). An additional 20 patients were monitored intraoperatively for plasma free Hb levels by a newly developed colorimetric method using a haptoglobin coated strip. Free Hb levels during CPB exceeded 30 mg/dl in 14 patients, who were immediately given haptoglobin. This treatment eliminated plasma free Hb within 30 minutes, and effectively prevented hemoglobinuria. Haptoglobin treatment brought significant decreases in the NAG index and alpha 1M index, suggesting a protective effect on renal function (Study 2).

Acetylglucosaminidase↗
PubMed1976

Association between macrophage activity and serum haptoglobin levels.

Serum haptoglobin is elevated by treatment of mice with thioglycollate, B.C.G. or silica. Haptoglobin concentrations were followed for a two week period following treatment and were found to correlate with the known effect of the stimulants upon macrophage activity. The numbers and characteristics of peritoneal exudate cells present following intraperitoneal thioglycollate inoculation suggest a relationship between phagocytic activity and serum haptoglobin levels and support the idea that serum haptoglobin levels may be controlled by mediators released during the process of phagocytosis.

Adjuvants, Immunologic↗
PubMed1991

Haptoglobin prevents renal dysfunction associated with intravariceal infusion of ethanolamine oleate.

Endoscopic injection sclerotherapy (EIS) with ethanolamine oleate was performed in patients with esophageal varices either with (18 patients) or without (19 patients) pretreatment with haptoglobin. The serum levels of urea nitrogen, creatinine, and beta 2-microglobulin, the creatinine clearance, and the urinary levels of N-acetyl-beta-D-glucosaminidase and urinary beta 2-microglobulin were measured before and after EIS. Indices of the glomerular filtration rate (serum levels of urea nitrogen, creatinine, beta 2-microglobulin; creatinine clearance) showed no significant changes after EIS in either the haptoglobin-treated or untreated groups. However, the increase in the urinary parameters after EIS (which are indices of renal tubular function) was suppressed in the haptoglobin-treated group (p less than 0.005 for urinary beta 2-microglobulin). Our results indicated that the administration of haptoglobin has a prophylactic effect on renal tubular dysfunction associated with the use of ethanolamine oleate in EIS.

Acute Kidney Injury↗