Heparin prevents antigen-induced airway hyperresponsiveness: Interference with IP3-mediated mast cell degranulation?

T. Ahmed, T. Syriste, R. Mendelssohn, D. Sorace, E. Mansour, M. Lansing, W. M. Abraham, M. J. Robinson

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

We hypothesized that heparin, because of its antiallergic and/or anti- inflammatory properties, modifies airway hyperresponsiveness (AHR). We studied the effects of inhaled heparin on AHR induced by specific antigen or by platelet-activating factor (PAF), a proinflammatory mediator. Specific lung resistance (sRL) was measured in 17 allergic sheep before, immediately after, and serially for up to 2 h after airway challenge with either specific antigen or PAF. Airway responsiveness was expressed as the cumulative provocative dose of carbachol that increased sRL to 4 cmH2O/s [PD4, in breath units (BU; 1 BU = 1 breath of 1% carbachol solution)]. PD4 was determined on a baseline day and on various experimental day 2 h after airway challenge with antigen or PAF, without or after pretreatment with inhaled heparin (1,000 U/kg). Pretreatment with inhaled heparin prevented antigen- induced bronchoconstriction and postantigen AHR. PD4 was 26 ± 2.6 (SE), 12 ± 1.7, and 22 ± 2.8 BU on baseline, antigen control, and postheparin days, respectively. Heparin given immediately after the antigen challenge failed to modify the magnitude and/or duration of antigen-induced bronchoconstrictor response or postantigen AHR. Heparin also failed to prevent PAF-induced changes in sRL and AHR. In vitro heparin inhibited anti-immunoglobin E- and 1,4,5-inositol triphosphate-mediated degranulation of rat peritoneal mast cells without attenuating the effects of the Ca2+ ionophore A-23187. These data suggest that in 'acute responders' heparin prevents antigen-induced bronchoconstriction and AHR, possibly by inhibiting 1,4,5-inositol triphosphate-dependent mast cell mediator release and not by its anti- inflammatory action.

Original languageEnglish (US)
Pages (from-to)893-901
Number of pages9
JournalJournal of applied physiology
Volume76
Issue number2
DOIs
StatePublished - 1994

Keywords

  • 1,4,5-inositol triphosphate
  • bronchial hyperreactivity
  • mast cell degranulation
  • mediator release
  • sheep

ASJC Scopus subject areas

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

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    Ahmed, T., Syriste, T., Mendelssohn, R., Sorace, D., Mansour, E., Lansing, M., Abraham, W. M., & Robinson, M. J. (1994). Heparin prevents antigen-induced airway hyperresponsiveness: Interference with IP3-mediated mast cell degranulation? Journal of applied physiology, 76(2), 893-901. https://doi.org/10.1152/jappl.1994.76.2.893