Abnormal mast cells in mice deficient in a heparin-synthesizing enzyme
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...
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Veröffentlicht in: | Nature (London) 1999-08, Vol.400 (6746), p.773-776 |
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Sprache: | eng |
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Zusammenfassung: | 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 (refs 4-7), 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. |
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ISSN: | 0028-0836 1476-4687 |
DOI: | 10.1038/23488 |