Effect of oral and intravenous heparin tetrasaccharide on allergic airway responses: Critical role of N-sulfation

Tahir Ahmed, Gregory Smith, William M. Abraham

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

We have shown that inhaled heparin (hep) oligosaccharides attenuate allergic airway responses in sheep and that this anti-allergic activity resides in a tetrasaccharide sequence. Here we determined: (a) the anti-allergic activity of oral and intravenous hep-tetrasaccharide on allergic airway responses in the sheep model of asthma; and (b) the role of N-sulfation in mediating this anti-allergic activity. Ascaris suum-induced early (EAR) and Late (LAR) airway responses and airway hyperresponsiveness (AHR) to carbachol were measured in allergic sheep without and after treatment with different doses of oral or intravenous hep-tetrasaccharide. At doses of 0.06 mg/kg, 0.125 mg/kg, and 0.25 mg/kg, oral hep-tetrasaccharide caused a dose-dependent inhibition of EAR and LAR. Post-antigen AHR was also inhibited dose dependently. The same doses of intravenous hep-tetrasaccharide yielded comparable inhibition of EAR, LAR and AHR, confirming that orally delivered hep-tetrasaccharide has good bioavailability. The protection by hep-tetrasaccharide on EAR and LAR was dependent on N-sulfation, as N-desulfated/N-acetylated tetrasaccharide had a markedly reduced effect. However, inhibition of the post-antigen AHR was independent of N-sulfation. These results demonstrate that orally administered hep-tetrasaccharide inhibits allergic airway responses in the sheep model of asthma. Hep-tetrasaccharide has good oral bioavailability and its anti-allergic activity is critically dependent on N-sulfation of the glucosamine ring.

Original languageEnglish (US)
Pages (from-to)180-188
Number of pages9
JournalPulmonary Pharmacology and Therapeutics
Volume26
Issue number2
DOIs
StatePublished - Apr 1 2013

Keywords

  • Heparin oligosaccharides
  • Inflammation
  • Oral bioavailability
  • Sheep asthma model

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Pharmacology (medical)
  • Biochemistry, medical

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