Abnormal mast cells in mice deficient in a heparin-synthesizing enzyme.
Nature
; 400(6746): 773-6, 1999 Aug 19.
Article
em En
| MEDLINE
| ID: mdl-10466727
ABSTRACT
Heparin is a sulphated polysaccharide, synthesized exclusively by connective-tissue-type mast cells and stored in the secretory granules in complex with histamine and various mast-cell proteases. Although heparin has long been used as an antithrombotic drug, endogenous heparin is not present in the blood, so it cannot have a physiological role in regulating blood coagulation. The biosynthesis of heparin involves a series of enzymatic reactions, including sulphation at various positions. The initial modification step, catalysed by the enzyme glucosaminyl N-deacetylase/N-sulphotransferase-2, NDST-2, is essential for the subsequent reactions. Here we report that mice carrying a targeted disruption of the gene encoding NDST-2 are unable to synthesize sulphated heparin. These NDST-2-deficient mice are viable and fertile but have fewer connective-tissue-type mast cells; these cells have an altered morphology and contain severely reduced amounts of histamine and mast-cell proteases. Our results indicate that one site of physiological action for heparin could be inside connective-tissue-type mast cells, where its absence results in severe defects in the secretory granules.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Heparina
/
Sulfotransferases
/
Amidoidrolases
/
Mastócitos
Idioma:
En
Ano de publicação:
1999
Tipo de documento:
Article