Inhibition of allergic airway responses by inhaled low-molecular-weight heparins: Molecular-weight dependence

José Martinez-Salas, Richard Mendelssohn, William M. Abraham, Bernard Hsiao, Tahir Ahmed

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Abstract

Inhaled heparin prevents antigent-induced bronchoconstriction and inhibits anti-immunoglobulin E-mediated mast cell degranulation. We hypothesized that the antiallergic action of heparin may be molecular weight dependent. Therefore, we studied the effects of three different low- molecular-weight fractions of heparin [medium-, low-, and ultralow-molecular- weight heparin (MMWH, LMWH, ULMWH, respectively)] on the antigen-induced acute bronchoconstrictor response (ABR) and airway hyperresponsiveness (AHR) in allergic sheep. Specific lung resistance was measured in 22 sheep before and after airway challenge with Ascaris suum antigen, without and after pretreatment with inhaled fractionated heparins at doses of 0.31-5.0 mg/kg. Airway responsiveness was estimated before and 2 h postantigen as the cumulative provocating dose of carbachol in breath units that increased specific lung resistance by 400%. All fractionated heparins caused a dose- dependent inhibition of ABR and AHR. ULMWH was the most effective fraction, with the inhibitory dose causing 50% protection (ID50) against ABR of 0.5 mg/kg, whereas ID50 values of LMWH and MMWH were 1.25 and 1.8 mg/kg, respectively. ULMWH was also the most effective fraction in attenuating AHR; the ID50 values for ULMWH, LMWH, and MMWH were 0.5, 2.5, and 4.7 mg/kg, respectively. These data suggest that 1) fractionated low-molecular-weight heparins attenuate antigen-induced ABR and AHR; 2) there is an inverse relationship between the antiallergic activity of heparin fractions and molecular weight; and 3) ULMWH is the most effective fraction preventing allergic bronchoconstriction and airway hyperresponsiveness.

Original languageEnglish (US)
Pages (from-to)222-228
Number of pages7
JournalJournal of applied physiology
Volume84
Issue number1
StatePublished - Jan 1 1998

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Keywords

  • Airway hyperresponsiveness
  • Mast cells

ASJC Scopus subject areas

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

Cite this

Martinez-Salas, J., Mendelssohn, R., Abraham, W. M., Hsiao, B., & Ahmed, T. (1998). Inhibition of allergic airway responses by inhaled low-molecular-weight heparins: Molecular-weight dependence. Journal of applied physiology, 84(1), 222-228.