Abnormal mast cells in mice deficient in a heparin-synthesizing enzyme

Sammanfattning

Heparin is a sulphated polysaccharide, synthesized exclusively by connective-tissue-type mast cells(1) and stored in the secretory granules in complex with histamine and various mast-cell proteases(2). 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(1,3). 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.

Publicerad i

Nature
1999, volym: 400, nummer: 6746, sidor: 773-776
Utgivare: MACMILLAN MAGAZINES LTD

SLU författare

• Pejler, Gunnar

  • Institutionen för veterinärmedicinsk kemi, Sveriges lantbruksuniversitet
    
  • Uppsala universitet

• Eriksson, Inger

  • Institutionen för veterinärmedicinsk kemi, Sveriges lantbruksuniversitet
    

• Kjellén, Lena

  • Institutionen för veterinärmedicinsk kemi, Sveriges lantbruksuniversitet
    

UKÄ forskningsämne

Cell- och molekylärbiologi
Immunologi inom det medicinska området

Publikationens identifierare

• DOI: https://doi.org/10.1038/23488

Permanent länk till denna sida (URI)

https://res.slu.se/id/publ/52775