Article (Scientific journals)
Deficiency in mouse hyaluronidase 2: a new mechanism of chronic thrombotic microangiopathy.
Onclinx, Cecile; Dogne, Sophie; Jadin, Laurence et al.
2015In Haematologica
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Keywords :
Red Cells; hemolysis; microangiopathy; thrombosis
Abstract :
[en] Hyaluronan is a major component of the extracellular matrix and glycocalyx. Its main somatic degrading enzymes are the hyaluronidases 1 and 2, none of which is active in the bloodstream. We generated hyaluronidase 2 deficient mice. They suffer from mild chronic anemia and thrombocytopenia, in parallel with a 10-fold increase in plasma hyaluronan concentration. The current study explores the mechanism of these hematological anomalies. The decreased erythrocyte and platelet counts were assigned to peripheral consumption. The erythrocyte half-life was reduced from 25 to 8 days without signs of premature aging. Hyaluronidase 2 deficient platelets were functional. Major intrinsic defects in erythrocyte membrane or stability, as well as detrimental effects of high hyaluronan levels on erythrocytes, were ruled out in vitro. Normal erythrocytes transfused into hyaluronidase 2 deficient mice were quickly destroyed but neither splenectomy nor anti-C5 administration prevented from chronic hemolysis. Schistocytes were present in hyaluronidase 2 deficient smears at a level of 1 to 6%, while virtually absent in control mice. Hyaluronidase 2 deficient mice had increased markers of endothelial damage and microvascular fibrin deposition, without renal failure, accumulation of ultra-large multimers of von Willebrand factor, deficiency of A Disintegrin And Metalloproteinase with ThromboSpondin type 1 motifs, member 13 (ADAMTS13), or hypertension. There was no sign of structural damage in hepatic or splenic sinusoids, or in any other microvessels. We conclude that hyaluronidase 2 deficiency induces chronic thrombotic microangiopathy with hemolytic anemia in mice. The link between this uncommon condition and hyaluronidase 2 remains to be explored in man.
Disciplines :
Hematology
Author, co-author :
Onclinx, Cecile
Dogne, Sophie
Jadin, Laurence
Andris, Fabienne
Grandfils, Christian ;  Université de Liège > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, et biochimie humaine
Jouret, François  ;  Université de Liège > Département des sciences cliniques > Néphrologie
Mullier, Francois
Flamion, Bruno
Language :
English
Title :
Deficiency in mouse hyaluronidase 2: a new mechanism of chronic thrombotic microangiopathy.
Publication date :
2015
Journal title :
Haematologica
ISSN :
0390-6078
eISSN :
1592-8721
Publisher :
Ferrata Storti Foundation, Italy
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2015, Ferrata Storti Foundation.
Available on ORBi :
since 06 June 2015

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