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PubMed2002

Upregulation of haptoglobin in reactive astrocytes after transient forebrain ischemia in rats.

Immunohistochemistry for haptoglobin (Hp) in the postischemic hippocampus demonstrated an immunoreactivity visible one day after reperfusion and continuing to increase until 14 days after ischemia. The immunoreactivity was most prominent in CA1 and the dentate hilar region, especially in cells with astroglial morphology. Double immunofluorescence histochemistry confirmed colocalization of the Hp and glial fibrillary acidic protein. Furthermore, a reverse transcription-polymerase chain reaction study confirmed an elevated Hp mRNA level in the postischemic hippocampus. The Hp gene expression was also upregulated in C6 and A-172 glioblastoma cell lines after H O treatment. These findings suggest that Hp is synthesized in reactive astrocytes in response to ischemia-reperfusion injury.

Animals↗
PubMed1984

Degradation of albumin, haemopexin, haptoglobin and transferrin, by black-pigmented Bacteroides species.

Strains of six black-pigmented Bacteroides species and one un-named strain were examined for their ability to degrade the plasma proteins albumin, haemopexin, haptoglobin and transferrin. Strains of B. gingivalis were most effective, degrading all four plasma proteins at different rates. Strains of B. intermedius and B. asaccharolyticus showed intermediate activities, degrading different individual plasma proteins; strains of B. melaninogenicus, B. loeschei and B. denticola were least active, degrading only haemopexin. These findings are discussed in relation to the availability in tissue fluids of iron for bacterial growth.

Bacteroides↗
PubMed1999

Crystallization of the haptoglobin-hemoglobin complex.

Two orthorhombic forms of crystals of the haptoglobin-hemoglobin complex were obtained using polyethylene glycol as precipitant. These crystals did not diffract well enough for data collection and work on the complex is no longer continued. However, the description of the crystallization conditions may be useful in future endeavors to obtain suitable crystals.

Chemical Precipitation↗
PubMed2005

Expression of haptoglobin in human keratinocytes and Langerhans cells.

BACKGROUND: Epidermal Langerhans cells (LCs) play an important role in cutaneous immunological reactions. Freshly obtained or intraepidermal LCs are incapable of activating autologous naive T cells. However, when they are cultured for 2-3 days, LCs are able to activate autologous T cells. It has been proposed that haptoglobin (Hp) is the inhibitor that prevents LC functional transformation in the skin. Abundant Hp has been found in the cytoplasm of epidermal LCs. However, the source of Hp in LCs has not been addressed. OBJECTIVES: To determine the expression of Hp in epidermal cells, and to provide evidence that there is a functional relationship between LCs and keratinocytes (KCs) through Hp. METHODS: Normal human epidermal cells and HaCaT cells were used for detection of Hp mRNA by in situ hybridization and reverse transcription-polymerase chain reaction, and Hp protein by immunohistochemical staining, immunofluorescence counterstaining and Western blotting. RESULTS: Hp mRNA was expressed in normal human KCs and HaCaT cells, but not in normal human epidermal LCs. Hp protein was detected by immunohistochemical staining and immunofluorescence counterstaining in CD1a+ epidermal dendritic cells (LCs), but not in KCs. Hp protein was weakly expressed by HaCaT cells. CONCLUSIONS: Hp mRNA is present in normal human KCs and HaCaT cells, suggesting that they have the potential to synthesize Hp protein. Normal human epidermal LCs are unable to synthesize Hp protein by themselves, although they have abundant Hp protein in their cytoplasm. It is likely that LCs acquire Hp through an exogenous pathway.

Adult↗
PubMed1991

Acute-phase protein synthesis in human hepatoma cells: differential regulation of serum amyloid A (SAA) and haptoglobin by interleukin-1 and interleukin-6.

Interleukin-6 (IL-6, BSF-2 or IFN-beta 2) is thought to be the major regulator of the acute-phase protein response that follows tissue injury and inflammation, with interleukin-1 (IL-1), tumour necrosis factor and more recently, LIF or HSF III, slightly stimulatory on only certain acute phase proteins. The synthesis of the major acute-phase protein SAA, originally described as being synthesized in response to IL-1, has been claimed recently to be mainly under IL-6 regulation. Our results show that in the human hepatoma cell line HuH-7, IL-1 is the major stimulating cytokine increasing SAA synthesis by a factor in excess of 100-fold. We also show that under most conditions interleukin-6 and tumour necrosis factor stimulate additively in combination with IL-1. Isoelectric focusing has demonstrated that SAA1 and SAA2 alpha are expressed but not SAA2 beta. The HuH-7 cell line is IL-6 responsive since haptoglobin is stimulated mainly by IL-6.

Acute-Phase Proteins↗
PubMed1997

Systemic acute-phase reactants, C-reactive protein and haptoglobin, in adult periodontitis.

Capture ELISAs with biotinylated monospecific antibodies were developed to detect both C-reactive protein (CRP) and haptoglobin (Hp) in serum of adult periodontitis (AP) patients and normal subjects. Each acute-phase reactant was significantly increased in serum from AP patients with CRP at 9.12 +/- 1.61 mg/l versus 2.17 +/- 0.41 mg/l (P < 0.001) and Hp at 3.68 +/- 0.37 g/l versus 1.12 +/- 0.78 g/l (P < 0.001). Assessment of clinical characteristics of the patients' periodontal disease indicated that CRP and Hp levels were significantly increased in patients with the most frequent disease active episodes (P < 0.02 and P < 0.001, respectively). Longitudinal examination of the Hp levels showed a significant decrease following scaling and root planing (3.68 versus 2.38 g/l; P < 0.01). After a 2-year administration of 50 mg/b.i.d. Flurbiprofen (a non-steroidal anti-inflammatory drug), significantly decreased Hp levels were noted (P < 0.005). CRP levels declined by 35-40% after 1-2 years of treatment with the drug (P < 0.05). The findings indicated that localized infections resulting in increased inflammation and tissue loss in the periodontium elicit systemic host changes manifest by increases in two acute-phase reactants. The conclusions are that either these molecules are formed locally and distributed to the serum, or these presumably localized infections impact upon the systemic components of the host protective responses.

Acute-Phase Proteins↗
PubMed2005

Limited influence of haptoglobin genotypes on severe malaria in Ghanaian children.

Haptoglobin (Hp) polymorphisms in sub-Saharan Africa have been associated with an increased risk of severe malaria. However, available data are inconclusive. We examined the role of Hp polymorphisms in susceptibility to Plasmodium falciparum infection and to severe malaria in northern Ghana. Three groups each of 290 age and sex-matched children with severe malaria, children with asymptomatic P. falciparum infection and aparasitaemic healthy controls were studied. Hp typing was based on PCR. In all children, Hp1-1, Hp2-1, and Hp2-2 occurred in 32.4%, 54.1%, and 13.5%, respectively. The prevalence of the Hp genotypes did not differ significantly between groups. However, Hp2 alleles were least common in healthy children (0.379), more frequent in parasitaemic controls (0.402), and most common in severe malaria patients (0.434; = 3.7; P = 0.06). In matched pair analysis, no Hp genotype increased the risk of severe malaria. However, using Hp1-1 as a reference, children with Hp2-2 exhibited a slightly increased risk of severe malaria (odds ratio, 1.6; P = 0.04). These results indicate that Hp polymorhisms may have a rather limited influence on the development of severe malaria.

Child↗
PubMed1976

An anomaly in the inheritance of haptoglobin types in Down's syndrome: a study of mother-child pairs.

A sample of 95 mother-child pairs provided evidence that plasma haptoglobin (Hp) types are inherited in an unusual manner by children with Down's syndrome. Homozygous mothers gave birth to more homozygotes and fewer heterozygotes than expected. Among offspring of heterozygous mothers, the frequencies were distributed essentially as expected. No abnormality was found in a normal control sample of 151 mother-child pairs. Using this material it was demonstrated that the anomalous Hp inheritance in Down's syndrome was not due simply to an increase in maternal age when the children were born.

Adolescent↗
PubMed1978

Local Shwartzman-like phenomenon prepared with haptoglobin-hemoglobin complex and provoked with prostaglandin.

Intradermal injection of haptoglobin-hemoglobin (Hp-Hb) complex followed by intravenous injection of prostaglandin (PG) F2a or E2 produced a local Shwartzman-like phenomenon (LSLP) in rabbits, whereas PGE1 has no provoking action. Intradermal injection of hemoglobin or erythrocytes also produced LSLP when provoked with endotoxin or PGF2alpha. The provoking action of endotoxin in the local shwartzman reaction may not be entirely mediated through PGs.

Animals↗
PubMed1975

Thermal and solvent perturbation as probes of conformational heterogeneity of haptoglobin 1-1.

The shifts which occur in the ultraviolet spectra of haptoglobin 1-1 (Hp) and a conformational isomer with lower affinity for hemoglobin (Hp), in response to temperature and solvent changes, have been measured by difference spectra. The thermal difference spectra provide evidence for a different participation of tryptophyl residues in the conformational stability of Hp and Hp. Solvent perturbations have allowed an estimation to be made of the number of surface chromophores in the native Hp and Hp. These results are compatible with the existence of two Hp conformational isomers with different free energy, separated by a high-potential barrier.

Animals↗
PubMed1975

Relationship of the biosynthesis of alpha-fetoprotein, albumin, hemopexin, and haptoglobin to the growth state of fetal rat hepatocyte cultures.

AFP and albumin are produced by arginine-synthesizing fetal rat hepatocytes in vitro. AFP and hemopexin production are coupled to hepatocellular proliferation, whereas albumin and haptoglobin production are not. During the cell cycle, AFP is synthesized prior to S and released prior to M. AFP may play a role in regulation of hepatocellular growth through estradiol binding and modulation of the intracellular concentration of lipoprotein (VLDL).

Albumins↗
PubMed2005

Haptoglobin concentrations in dogs undergoing trilostane treatment for hyperadrenocorticism.

BACKGROUND: Increased concentrations of haptoglobin (Hp), a moderate acute phase protein, have been demonstrated in dogs with hyperadrenocorticism (HAC). Monitoring serum concentrations of Hp in hyperadrenocorticoid dogs before and after trilostane administration may provide valuable information on the response to therapy. OBJECTIVE: The aim of this study was to measure Hp concentrations in dogs with spontaneously occurring HAC at the time of diagnosis and after treatment with trilostane. METHODS: Serum Hp concentration was measured using an automatic biochemical assay based on Hp-hemoglobin binding and utilizing SB-7 reagent in 12 dogs with spontaneous HAC before and after treatment with trilostane (30 or 60 mg PO q 12-24 h). Post-treatment Hp concentrations were measured at the time the owner reported an improvement in clinical signs. Pretreatment and post-treatment Hp values were compared with reference values and with values from 4 healthy control dogs. RESULTS: Two dogs with HAC had pretreatment Hp values within the reference interval; 10 dogs had moderate (n = 8) or marked (n = 2) increases in Hp concentration. After treatment with trilostane, Hp concentration remained within the reference interval (n = 2), decreased to within the reference interval (n = 3), or remained moderately increased (n = 7; 3-10 g/L). Overall, a significant decrease was observed in Hp concentration after trilostane treatment compared with pretreatment values (P <.005). Both untreated and treated dogs with HAC had significantly higher Hp concentrations (P <.001) when compared with control dogs. CONCLUSIONS: Clinical control of HAC did not closely relate to serum Hp concentration. Further studies are required to assess whether this is because of inadequate control of disease or because a build-up of cortisol precursors or secondary effects of HAC affect Hp concentration.

Adrenocortical Hyperfunction↗
PubMed1968

Haptoglobin and catalase loci in man: possible genetic linkage.

Slow- and fast-migrating electrophoretic variants of human erythrocyte catalase were encountered in four of approximately 200 families. Tests for nine genetic polymorphisms provided evidence suggesting linkage only in the case of the haptoglobin system.

Catalase↗
PubMed1970

Heritable fragile site on chromosome 16: probable localization of haptoglobin locus in man.

We have found recurrent chromosome breaks at a site (the "fragile site") on the long arm of chromosome 16. This site segregates in simple Mendelian dominant fashion in a large family. The distal portion of the chromosome sometimes shows selective endoreduplication. Preliminary linkage results reveal only 3 recombinants in 33 opportunities for recombination between the fragile site and the alpha locus of haptoglobin, an indication that the alpha-Hp gene is located near this region on chromosome 16.

Adolescent↗
PubMed1984

Role of heme compounds and haptoglobin in Vibrio vulnificus pathogenicity.

An induced peritonitis model was employed in mice to determine whether heme-containing molecules enhance the lethality of infections by Vibrio vulnificus. The lethality of intraperitoneal (ip) inocula of the bacteria was increased by concurrent injections (ip) of hemoglobin, methemoglobin, or hematin, but not by myoglobin. Similar results were obtained in mice with phenylhydrazine-induced hemoglobinemia, in which after ip injections of V. vulnificus, a direct correlation between lethality and levels of plasma hemoglobin was observed. In vitro studies indicated that the growth of V. vulnificus, which was limited in an iron-poor medium, was enhanced by the addition of hemoglobin in a manner similar to an inorganic iron source, ferric ammonium citrate. These results suggest that V. vulnificus is capable of extracting iron from hemoglobin for use as a nutrilite, thereby promoting growth and increased lethality in the in vivo models. Further studies with human serum cultures demonstrated that the growth of V. vulnificus was not decreased when hemoglobin added to the serum was completely complexed with haptoglobin; these results are in opposition to those with cultures of Escherichia coli. These results are discussed relative to the capacity of V. vulnificus to produce fatal human infections.

Animals↗
PubMed1988

Ability of Vibrio vulnificus to obtain iron from hemoglobin-haptoglobin complexes.

It has been suggested that the normal serum protein, haptoglobin (Hp), serves a bacteriostatic role by binding free hemoglobin (Hm), thus making heme iron unavailable for bacterial growth. Previous studies showed that, unlike Escherichia coli, Vibrio vulnificus was able to overcome this Hp-blocking effect. We report here a study on the iron-withholding property of the three major human Hp phenotypes, Hp 1, 2, and 2-1. Results of experiments with human serum showed that V. vulnificus C7184 was able to obtain iron from Hm bound to Hp types 1 and 2, but not that bound to Hp 2-1. E. coli 2395-80, on the other hand, was unable to overcome the blocking effect of any Hp phenotype. Using purified Hp 1, we also demonstrated that, although V. vulnificus was unable to grow in a deferrated medium without an additional iron source, it was able to grow with the addition of the Hm-Hp complex.

Haptoglobins↗