Immunological and Biochemical Investigations of Human Serum Haptoglobin: Composition of Haptoglobin–Haemoglobin Intermediate, Haemoglobin-Binding Sites and Presence of Additional Alleles for β-Chain

Shim, Bong-Sop; Lee, Tong-Ho; Kang, Young‐Hoon

doi:10.1038/2071264a0

Cited by 50 publications

(9 citation statements)

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“…52,59 Hence, the Hp1-1 molecule is able to bind 2 Hb ␣␤-dimers (Figure 3), whereas the Hp2-1 and Hp2-2 may be able to bind several Hb ␣␤-dimers. [53][54][55][56][60][61][62][63][64][65] Besides having a direct inhibitory effect on the toxic properties of Hb, as well as preventing peroxidative modification of Hb, 66 Hp highly expedites Hb clearance, leading to production of anti-inflammatory metabolites. 67 The fast removal of Hp-Hb complexes is explained by the high-affinity binding to the 130-kDa transmembrane receptor CD163 expressed in monocytes and macrophages.…”

Section: Haptoglobin: a Hemoglobin Scavenger Facilitating The Anti-inmentioning

confidence: 99%

“…50,51 The main function of the Hp ␣-chains appears to be connection of (␣␤)-units to form dimers (Hp1-1 and Hp2-2 phenotypes) and multimers (Hp2-1 and Hp2-2 phenotypes), 2,52 whereas the interaction with other proteins, including Hb and CD163, is mediated by the larger and more accessible ␤-chain. 48,49,[52][53][54][55][56] The latter chain is generally more conserved between species than is the ␣-chain 57 and lacks the catalytic triad of genuine serine proteases. 47 Accordingly, no proteolytic activity has been assigned to Hp.…”

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confidence: 99%

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Receptor targeting of hemoglobin mediated by the haptoglobins: roles beyond heme scavenging

Nielsen

Moestrup

2009

Blood

138

109

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Haptoglobin, the haptoglobin-hemoglobin receptor CD163, and the heme oxygenase-1 are proteins with a well-established function in the clearance and metabolism of "free" hemoglobin released during intravascular hemolysis. This scavenging system counteracts the potentially harmful oxidative and NO-scavenging effects associated with "free" hemoglobin, and, furthermore, elicits an anti-inflammatory response. In the late primate evolution, haptoglobin variants with distinct functions have arisen, including haptoglobin polymers and the haptoglobin-related protein. The latter associates with a subspecies of high-density lipoprotein (HDL) particles playing a crucial role in the innate immunity against certain trypanosome parasites. Recent studies have elucidated this fairly sophisticated immune defense mechanism that takes advantage of a trypanosomal haptoglobin-hemoglobin receptor evolved to supply the parasite with heme. Because of the high resemblance between haptoglobin and haptoglobinrelated protein, the receptor also takes up the complex of hemoglobin and the HDL- IntroductionHaptoglobin (Hp), an abundant acute phase plasma glycoprotein of the ␣ 2 -globulin fraction, was initially reported in 1938 by Polonovski and Jayle to be a "plasma substance" that binds hemoglobin (Hb). 1 In agreement with this initial characterization and its designation as "haptoglobin" (Greek: haptein, "to bind" ϩ [hemo]globin), Hp has a well-established role in binding of "free" Hb released into the circulation during the process of intravascular hemolysis. By capturing the liberated Hb, Hp protects against toxic effects associated with Hb, and it facilitates Hb clearance through endocytosis by the macrophage scavenger receptor CD163. 2 Later studies of human and primate plasma revealed variant forms of Hp as well as the existence of an Hp-related protein (Hpr) that recently has been shown also to bind Hb. As highlighted in this review, novel functions of Hp depend on high-affinity interactions with Hb and lipoprotein and subsequent receptor recognition of the resulting complexes. Toxicity of hemoglobin released during intracellular hemolysisIntravascular hemolysis, which accounts for approximately 10% to 20% of total red blood cell destruction, 3 changes Hb from being an intracellular O 2 /CO 2 transporter to a highly toxic substance in plasma. This toxicity arises from the heme iron, which can react with endogenous hydrogen peroxide to produce free radicals, which in turn may cause severe oxidative tissue damage, 4 particularly in the kidney. 5 In addition to the oxidative toxicity of Hb, Hb is a potent scavenger of nitric oxide (NO), a signaling molecule that functions as a critical regulator of smooth muscle relaxation, endothelial adhesion molecule expression, and platelet activation and aggregation. 6,7 The reaction of Hb with NO is fast and irreversible, leading to the production of nitrate and methemoglobin. If allowed to occur, this Hbmediated consumption of vascular NO, referred to as NOscavenging, thus limits the bioavailabili...

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Section: Haptoglobin: a Hemoglobin Scavenger Facilitating The Anti-inmentioning

confidence: 99%

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confidence: 99%

Receptor targeting of hemoglobin mediated by the haptoglobins: roles beyond heme scavenging

Nielsen

Moestrup

2009

Blood

138

109

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“…Hp 1-1 type, a monomeric form, is a tetrachain structure composed of two 1 and two polypeptides. 2,5,6 Hp 2-1 and Hp 2-2 types are polymeric forms of higher molecular mass, which contain 1 , 2 and chains, and 2 and chains, respectively. 2,6 Haptoglobin phenotypes are determined by two alleles, Hp 1 and Hp 2 .…”

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Distribution of haptoglobin phenotypes in a Korean population, using the semi-automated PhastSystem

Yang

Min²,

Park³

et al. 2000

Ann Clin Biochem

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SUMMARY.We have established a new phenotyping method for haptoglobin, based on sodium dodecyl sulphate±polyacrylamide gel electrophoresis using the PhastSystem (Pharmacia Biotech, Uppsala, Sweden), followed by immunoblotting for detection. We measured haptoglobin concentrations and determined the haptoglobin phenotypes of 316 healthy Koreans using this method: 31 (9´8%) were of Hp 1-1 type, 140 (44´3%) of Hp 2-1 type and 145 (45´9%) of Hp 2-2 type. The haptoglobin allele frequencies were calculated to be 0´32 for Hp 1 and 0´68 for Hp 2 . We were able to visualize up to 12 bands from the human Hp 2-2 polymeric series, with molecular weights in the range 171´9 10 3 to 802´2 10 3 . The reference range of serum haptoglobin concentrations obtained by the IFCC (International Federation of Clinical Chemistry) standard method was 0´27±2´14 g/L. The serum haptoglobin concentration in Koreans was similar to that of Caucasians, but the Hp 1 allele frequency was lower in Koreans. Our method could be used in clinical laboratories as a simple and practical method of haptoglobin phenotyping. In addition, the Hp 2-2 polymeric series could be used as high molecular weight standards.Haptoglobin is a glycoprotein that is expressed by a genetic polymorphism as three major phenotypes: Hp 1-1, Hp 2-1 and Hp 2-2.

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“…On the other hand antisera against Hp 2-2 readily produce spurs [15,24], S h im et a/. [35] demonstrated that antibodies against the //-chain of haptoglobin reacted with free but not with hemoglobin saturated haptoglobin, while antibodies against the a-chain reacted with haptoglobin regardless of whether or not hemoglobin was present. Their conclusion that hemoglobin binds to the//-chain of haptoglobin was later confirmed by G o r d o n and Bea r n [18] by direct measure ment of the hemoglobin binding capacity of the isolated //-chains.…”

Section: Discussionmentioning

confidence: 99%

Subtyping Haptoglobins with Precipitating Antisera

Ehnholm

1969

Int Arch Allergy Immunol

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Immunological and Biochemical Investigations of Human Serum Haptoglobin: Composition of Haptoglobin–Haemoglobin Intermediate, Haemoglobin-Binding Sites and Presence of Additional Alleles for β-Chain

Cited by 50 publications

References 12 publications

Receptor targeting of hemoglobin mediated by the haptoglobins: roles beyond heme scavenging

Receptor targeting of hemoglobin mediated by the haptoglobins: roles beyond heme scavenging

Distribution of haptoglobin phenotypes in a Korean population, using the semi-automated PhastSystem

Subtyping Haptoglobins with Precipitating Antisera

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