Haptoglobin halts hemoglobin’s havoc

Kato, Gregory J.

doi:10.1172/jci40258

Cited by 41 publications

(49 citation statements)

References 21 publications

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“…Hp provides the first line of defense against extracellular Hb. 13 When bound to Hp, Hb remains sequestered within the intravascular compartment, thus attenuating Hb-mediated vasoactivity, oxidative toxicity, and tissue peroxidation. 14,15 Upon complex formation, Hp transforms the Hb ␣␤-dimer into a high-affinity ligand of the Hb scavenger receptor CD163, which then clears the Hb:Hp complex.…”

Section: Introductionmentioning

confidence: 99%

Glucocorticoid treatment skews human monocyte differentiation into a hemoglobin-clearance phenotype with enhanced heme-iron recycling and antioxidant capacity

Vallelian

Schaer²,

Kaempfer³

et al. 2010

Blood

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Glucocorticoids are used extensively to treat autoimmune hemolytic anemias. Some beneficial effects of glucocorticoid pulse therapy have also been reported in sickle cell disease and paroxysmal nocturnal hemoglobinuria. Based on established concepts of hemoglobin (Hb) toxicity and physiologic Hb scavenger systems, we evaluated whether glucocorticoids could support an adaptive response to extracellular Hb independently of their immunosuppressive activities. Using global proteome and transcriptome analysis with mass-spectrometry (isobaric tag for relative and absolute quantitation and liquid chromatography-mass spectrometry) and gene-array experiments, we found that glucocorticoid treatment in vitro and in patients on glucocorticoid-pulse therapy polarized monocytes into a M2/alternatively activated phenotype with high Hb-scavenger receptor (CD163) expression and enhanced Hbclearance and detoxification capability. Monocytes concurrently exposed to the interactive activity of glucocorticoids and extracellular Hb were characterized by high expression of a group of antioxidant enzymes known to be regulated by the conserved oxidative response transcription factor nuclear factor E2-related factor. Further, suppressed transferrin receptor, together with high ferroportin expression, pointed to a shift in iron homeostasis directed toward an increased cellular export of heme-derived iron. Therefore, stimulating Hb-endocytosis by CD163 and enhancing antioxidative homeostasis and iron recycling may be an essential activity of glucocorticoids that helps alleviate the adverse effects of extracellular Hb. (Blood. 2010;116(24):5347-5356) IntroductionGlucocorticoids are used extensively to treat inflammatory and autoimmune diseases. In autoimmune hemolytic anemia, glucocorticoids are thought to attenuate the production of erythrocytedirected autoantibodies while reducing destruction of immunoglobulin-coated red blood cells by macrophages within the reticuloendothelial system. 1 Intriguingly, randomized clinical trials demonstrated that glucocorticoid pulse therapy also has short-term beneficial effects on complications of nonimmune hemolysis such as acute chest syndrome and pain crisis in children with sickle cell disease. 2,3 Likewise, glucocorticoid treatment of paroxysmal nocturnal hemoglobinuria (PNH) has been advocated to attenuate the severity of hemolytic crisis by not yet established mechanisms. 4 Glucocorticoid treatment of PNH and sickle cell complications is controversial due to the high incidence of treatment-associated complications and rebound attacks. [4][5][6] Nevertheless, these studies could suggest that glucocorticoids might enhance the level of protection against extracellular hemoglobin (Hb) exposure that occurs during nonimmune intravascular hemolysis in PNH and sickle cell disease. In addition, in autoimmune hemolytic anemia plasma, haptoglobin (Hp) is usually consumed pointing to the leakage of free Hb into the circulation.Extracellular Hb has been associated with toxic adverse effects. 7 Free radicals and...

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Section: Introductionmentioning

confidence: 99%

Glucocorticoid treatment skews human monocyte differentiation into a hemoglobin-clearance phenotype with enhanced heme-iron recycling and antioxidant capacity

Vallelian

Schaer²,

Kaempfer³

et al. 2010

Blood

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“…Therefore, the removal of liberated Hb represents a useful strategy for therapeutic intervention in both systemic hemolysis and diseases that are related to local hemolysis. So far, it has been established that Hp provides the first defense line against extracellular Hb by forming an Hb-Hp complex (5) and that CD163 plays a crucial role as a scavenger receptor for Hb-Hp complexes. However, the functional roles of other acute phase proteins in hemolysis are not known with certainty.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, the body has developed a system that efficiently scavenges Hb liberated from erythrocytes. Haptoglobin (Hp), 2 an acute phase plasma protein, provides the first line of defense against the effects of liberated Hb (5). When Hb binds to Hp, Hb remains sequestered within the intravascular compartment, thus attenuating Hb-mediated vasoactivity, oxidative toxicity, and tissue peroxidation (6,7).…”

mentioning

confidence: 99%

α1-Acid Glycoprotein Up-regulates CD163 via TLR4/CD14 Protein Pathway

Komori

Watanabe

Shuto

et al. 2012

Journal of Biological Chemistry

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“…However, we do not know whether the rapid changes in apolipoprotein A-IV precursor after FMDV infection can cause similar pathological phenomena. Haptoglobin possesses antioxidant activity towards hemoglobin-stimulated lipid peroxidation and halts hemoglobin's havoc as well [13]. According to the study of Boretti et al [6], haptoglobin induction might occur as part of the glucocorticoid-induced compensatory response to inflammation, in addition to induction of CD163 and CD91 [15].…”

Section: Discussionmentioning

confidence: 99%

Proteomics Analysis of Porcine Serum Proteins by LC-MS/MS after Foot-and-Mouth Disease Virus (FMDV) Infection

Liu

Zhang

Zheng

et al. 2011

The Journal of Veterinary Medical Science

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ABSTRACT. To analyze serum proteomics differences between normal and foot and mouth disease virus (FMDV)-infected piglets, an analytical method based on liquid chromatography with tandem mass spectrometry (LC-MS/MS) was used. Samples of venous blood were collected before and after FMDV infection and high abundance serum albumin was removed using a commercial kit. After trypsin digestion, serum samples were processed with LC-MS/MS. Proteins were identified by peptide mass fingerprinting. We found that apolipoprotein A-IV precursor, haptoglobin and probable chemoreceptor glutamine deamidase cheD appeared after FMDV infection in the same piglet. This is believed to be the first time that serum proteomics analysis by LC-MS/MS after FMDV infection has been performed, and our results may provide further information about biomarkers for early diagnosis of FMD in piglets.KEY WORDS: foot and mouth disease virus infection, liquid chromatography-tandem mass spectrometry, porcine serum, proteomics analysis.J. Vet. Med. Sci. 73(12): 1569-1572, 2011 Recent determination of the sequence of the foot and mouth disease virus (FMDV) genome has led to greater understanding of the structure and function of the virus genome. However, genome informatics cannot predict mRNA content and the degree of protein modification. Furthermore, relativity between mRNA and proteins is very low [7]. Therefore, research into the pathogenic mechanism of FMD at the genomic level alone has major limitations. For successful invasion and replication in the host, FMDV needs to overcome the immune response and block the normal cell cycle of the host, and synthesize itself by utilizing materials and energy of the host cells. Interactions between viruses and their hosts are accompanied by changes in host gene expression profile. This affects the normal physiological function of the host, and determines and reflects the infection-associated pathogenic processes and outcomes. The development of proteomic technology has revolutionized our ability to assess protein changes on a global scale [16]. Hence, a comprehensive study of the interaction between FMDV and its host is needed at the proteomic level [25], however, there is no reference to this in the literature.Serum is an attractive source of protein or peptide biomarkers [8]. Serum and plasma samples are easy to collect, even repeatedly, and have the advantages of high protein content and containing the proteins in a highly soluble form [18]. In addition, serum possesses a large number of proteins that are related to overall pathophysiology. Alterations in proteomic patterns with regard to composition, function and structure of serum proteins can serve to indicate pathological abnormalities even before clinical symptoms are observed. These changes directly influence the progress of disease [2,12]. Therefore, studies of dynamic variations in proteins or biomarkers from serum may provide more significant information for unraveling the mechanisms of disease and discovering biomarkers associated with new drug ta...

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Haptoglobin halts hemoglobin’s havoc

Cited by 41 publications

References 21 publications

Glucocorticoid treatment skews human monocyte differentiation into a hemoglobin-clearance phenotype with enhanced heme-iron recycling and antioxidant capacity

Glucocorticoid treatment skews human monocyte differentiation into a hemoglobin-clearance phenotype with enhanced heme-iron recycling and antioxidant capacity

α1-Acid Glycoprotein Up-regulates CD163 via TLR4/CD14 Protein Pathway

Proteomics Analysis of Porcine Serum Proteins by LC-MS/MS after Foot-and-Mouth Disease Virus (FMDV) Infection

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