Molecular-weight-dependent effects of nonanticoagulant heparins on allergic airway responses

Carlos Campo, Jussara F. Molinari, Jaime Ungo, Tahir Ahmed

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

We have hypothesized that antiallergic activity of inhaled heparin is molecular weight dependent and mediated by 'nonanticoagulant fractions' (NAF- heparin). Therefore, we studied comparative effects of high-, medium-, and ultralow-molecular-weight (HMW, MMW, and ULMW, respectively) NAF-heparins on acute bronchoconstrictor response (ABR) and airway hyperresponsiveness (AHR) in allergic sheep. Specific lung resistance was measured in 23 allergic sheep, before and immediately after challenge with Ascaris suum antigen, without and after pretreatment with inhaled NAF-heparins. Airway responsiveness was estimated before and 2 h postantigen as the cumulative provocating dose of carbachol in breath units, which increased specific lung resistance by 400%. NAF-heparins attenuated ABR and AHR in a molecular- weight-dependent fashion. HMW NAF-heparin (n = 8) was the least effective agent: it attenuated ABR [inhibitory dose causing 50% protection (ID50) = 4 mg/kg] but had no effect on AHR. MMW NAF-heparin (n = 8) showed intermediate efficacy (ABR ID50 = 0.8 mg/kg, AHR ID50 = 1.4 mg/kg), whereas ULMW NAF- heparin (n = 7) was the most effective agent (ABR ID50 = 0.4 mg/kg, AHR ID50 = 0.2 mg/kg). ULMW NAF-heparin was 3.5 times more potent in attenuating antigen-induced AHR when administered 'after' antigen challenge and failed to inhibit the bronchoconstrictor response to carbachol and histamine. In 15 additional sheep, segmental antigen challenge caused a marked increase in histamine in bronchoalveolar lavage fluid that was not prevented by any of the inhaled NAF-heparins. These data indicate that antiallergic activity of inhaled heparin is independent of its anticoagulant action and resides in the <2,500 ULMW chains. The antiallergic activity of NAF-heparins is mediated by an unknown biological action and may have therapeutic potential.

Original languageEnglish
Pages (from-to)549-557
Number of pages9
JournalJournal of Applied Physiology
Volume86
Issue number2
StatePublished - Feb 1 1999
Externally publishedYes

Fingerprint

Heparin
Molecular Weight
Bronchoconstrictor Agents
Anti-Allergic Agents
Antigens
Sheep
Carbachol
Histamine
Ascaris suum
Lung
Bronchoalveolar Lavage Fluid
Anticoagulants

Keywords

  • Airway hyperresponsiveness
  • Antigen-induced bronchoconstriction
  • Asthma

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

Cite this

Molecular-weight-dependent effects of nonanticoagulant heparins on allergic airway responses. / Campo, Carlos; Molinari, Jussara F.; Ungo, Jaime; Ahmed, Tahir.

In: Journal of Applied Physiology, Vol. 86, No. 2, 01.02.1999, p. 549-557.

Research output: Contribution to journalArticle

Campo, C, Molinari, JF, Ungo, J & Ahmed, T 1999, 'Molecular-weight-dependent effects of nonanticoagulant heparins on allergic airway responses', Journal of Applied Physiology, vol. 86, no. 2, pp. 549-557.
Campo, Carlos ; Molinari, Jussara F. ; Ungo, Jaime ; Ahmed, Tahir. / Molecular-weight-dependent effects of nonanticoagulant heparins on allergic airway responses. In: Journal of Applied Physiology. 1999 ; Vol. 86, No. 2. pp. 549-557.
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