Glycophorin A‐mediated haemolysis of normal human erythrocytes: evidence for antigen aggregation in the pathogenesis of immune haemolysis

Brain, M. C.; Prevost, Jay; Pihl, Carin; Brown, Christopher B.

doi:10.1046/j.1365-2141.2002.03657.x

Cited by 24 publications

(29 citation statements)

References 39 publications

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“…K ؉ efflux. K ϩ efflux was measured by atomic absorption spectrometry (model AA-6800 instrument; Shimadzu, Kyoto, Japan) as described previously (6,14,16). In brief, red blood cells were suspended at 1% in 5 mM HEPES-0.15 M NaCl buffer without K ϩ .…”

Section: Methodsmentioning

confidence: 99%

Hemolysis of Erythrocytes by Granulysin-Derived Peptides but Not by Granulysin

Dong

Deng

et al. 2005

Antimicrob Agents Chemother

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Granulysin, a 9-kDa protein localized in human cytolytic T lymphoctyes and natural killer cell granules, is cytolytic against tumors and microbes but not against red blood cells. Synthetic peptides corresponding to the central region of granulysin recapitulate the lytic activity of the intact molecule, and some peptides cause hemolysis of red blood cells. Peptides in which cysteine residues were replaced by serine maintain their activity against microbes but lose activity against human cells, suggesting their potential as antibiotics. Studies were undertaken to determine the mechanism of resistance of red blood cells to granulysin and sensitivity to a subset of granulysin-derived peptides. Granulysin lyses immature reticulocytes, which have mitochondria, but not red blood cells. Granulysin lyses U937 cells but not U937 cells lacking mitochondrial DNA and a functional respiratory chain (U937°cells), further demonstrating the requirement of intact mitochondria for granulysinmediated death. Peptide G8, which corresponds to helix 2/loop 2/helix 3, lyses red blood cells, while peptide G9, which is identical except that the cysteine residues were replaced by serine, does not lyse red blood cells. Granulysin peptide-induced hemolysis is markedly inhibited by an anion transporter inhibitor and by Na ؉ , K ؉ , and Ca 2؉ channel blockers but not by Na ؉ /K ؉ pump, cotransport, or Cl ؊ channel blockers. Although recombinant granulysin and G9 peptide do not induce hemolysis, they both competitively inhibit G8-induced hemolysis. The finding that some derivatives of granulysin are hemolytic may have important implications for the design of granulysin-based antimicrobial therapeutics.

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Section: Methodsmentioning

confidence: 99%

Hemolysis of Erythrocytes by Granulysin-Derived Peptides but Not by Granulysin

Dong

Deng

et al. 2005

Antimicrob Agents Chemother

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“…Finding IgG-induced hemoglobinuria in C3-deficient mice is surprising, but may result from the ability of some anti-hGPA antibodies to destabilize RBC phospholipid bilayers, thereby inducing hemolysis. 16 In addition, the ability of thrombin to cleave C5 in C3 KO mice may provide another explanation for this phenomenon. 17 …”

Section: Transfused Incompatible Rbcs Are Rapidly Cleared In Passivelmentioning

confidence: 99%

Cytokine storm in a mouse model of IgG-mediated hemolytic transfusion reactions

Hod

Cadwell

Liepkalns

et al. 2008

Blood

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“…54,55 Antibodies to hGPA antigens cause HTRs, 56 hemolytic disease of the newborn, 57 and AIHA. 55,58,59 The hGPA-Tg mouse provides a genetically inheritable, murine "blood group system." Thus, wild-type mRBCs are "antigennegative" and hGPA-Tg-mRBCs are "antigen positive."…”

Section: The Relevance Of Tg Hgpa For Immune-mediated Hemolysismentioning

confidence: 99%

Mouse models of IgG- and IgM-mediated hemolysis

Schirmer

Song

Baliff

et al. 2006

Blood

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Well-characterized mouse models of alloimmune antibody-mediated hemolysis would provide a valuable approach for gaining greater insight into the pathophysiology of hemolytic transfusion reactions. To this end, mouse red blood cells (mRBCs) from human glycophorin A transgenic (hGPA-Tg) donor mice were transfused into non-Tg recipients that had been passively immunized with IgG or IgM hGPA-specific monoclonal antibodies (mAbs). In this novel murine "blood group system," mRBCs from hGPA-Tg IntroductionHemolytic transfusion reactions (HTRs) are dangerous complications of blood transfusions. IgM-mediated HTRs (IgM-HTRs) occur acutely, are usually due to ABO incompatibility, typically cause intravascular hemolysis, and can lead to shock, renal failure, coagulopathy, and death. 1 Although infrequent, IgM-HTRs have a high mortality rate. IgG-mediated HTRs (IgG-HTRs) are more common, but usually less severe, than IgM-HTRs; they can occur acutely or be delayed, typically cause extravascular hemolysis, and occasionally result in renal failure, coagulopathy, and death. 2 Symptomatic immune-mediated red blood cell (RBC) destruction also occurs in autoimmune hemolytic anemia (AIHA), 3 blood group incompatible transplantation, 4 and immune thrombocytopenic purpura (ITP) treated with Rh-immune globulin. 5 Although various different modalities are used to treat HTRs, there is no definitive evidence regarding efficacy. Given the sporadic nature of HTRs, designing human trials to evaluate treatment options is difficult. Therefore, to study the mechanisms underlying HTRs, to evaluate the efficacy of existing treatments, and to develop new treatments, a relevant, inexpensive, and tractable animal model is required. 6 A mouse model would be ideal for this purpose, 7 given the abundance of reagents and relevant knockout (KO) and transgenic (Tg) animals. Although mouse blood group polymorphisms exist, 8 and transfused incompatible mouse RBC (mRBCs) are rapidly cleared, 9,10 no one has exploited these findings to develop a model of HTRs. The availability of a Tg mouse expressing human glycophorin A (hGPA; gene symbol designation, GYPA) on mRBCs 11 offers an approach using a well-described glycoprotein target and well-characterized reagents.We describe initial studies validating mouse models of IgG-and IgM-mediated alloimmune hemolysis. Thus, mRBCs from hGPA-Tg donors were transfused into non-Tg recipients that were passively immunized with IgG or IgM hGPA-specific monoclonal antibodies (mAbs). The clearance of the transfused mRBCs was quantified and the roles of complement and Fc␥ receptors were evaluated. Materials and methods AntibodiesPurified mAbs NaM10-2H12 (IgG3), NaM26-3F4 (IgG1), and NaM10-6G4 (IgG2a), which recognize peptide epitopes on the M and N forms of hGPA, 12 were purchased from EFS (Nantes, France). Hybridomas producing mAb 6A7, an IgG1 specific for a sialic acid-dependent epitope on M-type hGPA, 13-15 10F7, an IgG1 recognizing a nonpolymorphic epitope on hGPA, 13,14 and J11d, a rat IgM recognizing CD24 on mRBCs, 16,17...

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Glycophorin A‐mediated haemolysis of normal human erythrocytes: evidence for antigen aggregation in the pathogenesis of immune haemolysis

Cited by 24 publications

References 39 publications

Hemolysis of Erythrocytes by Granulysin-Derived Peptides but Not by Granulysin

Hemolysis of Erythrocytes by Granulysin-Derived Peptides but Not by Granulysin

Cytokine storm in a mouse model of IgG-mediated hemolytic transfusion reactions

Mouse models of IgG- and IgM-mediated hemolysis

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