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

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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
Pages (from-to)893-901
Number of pages9
JournalJournal of Applied Physiology
Volume76
Issue number2
StatePublished - Jan 1 1994
Externally publishedYes

Fingerprint

Cell Degranulation
Mast Cells
Heparin
Antigens
Platelet Activating Factor
Inositol 1,4,5-Trisphosphate
Bronchoconstriction
Carbachol
Anti-Inflammatory Agents
Bronchoconstrictor Agents
Anti-Allergic Agents
Ionophores
Calcimycin
Sheep
Lung

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

Cite this

Ahmed, T., Syriste, T., Mendelssohn, R., Sorace, D., Mansour, E., Lansing, 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.

Heparin prevents antigen-induced airway hyperresponsiveness : Interference with IP3-mediated mast cell degranulation? / Ahmed, T.; Syriste, T.; Mendelssohn, R.; Sorace, D.; Mansour, E.; Lansing, M.; Abraham, W. M.; Robinson, M. J.

In: Journal of Applied Physiology, Vol. 76, No. 2, 01.01.1994, p. 893-901.

Research output: Contribution to journalArticle

Ahmed, T, Syriste, T, Mendelssohn, R, Sorace, D, Mansour, E, Lansing, M, Abraham, WM & Robinson, MJ 1994, 'Heparin prevents antigen-induced airway hyperresponsiveness: Interference with IP3-mediated mast cell degranulation?', Journal of Applied Physiology, vol. 76, no. 2, pp. 893-901.
Ahmed T, Syriste T, Mendelssohn R, Sorace D, Mansour E, Lansing M et al. Heparin prevents antigen-induced airway hyperresponsiveness: Interference with IP3-mediated mast cell degranulation? Journal of Applied Physiology. 1994 Jan 1;76(2):893-901.
Ahmed, T. ; Syriste, T. ; Mendelssohn, R. ; Sorace, D. ; Mansour, E. ; Lansing, M. ; Abraham, W. M. ; Robinson, M. J. / Heparin prevents antigen-induced airway hyperresponsiveness : Interference with IP3-mediated mast cell degranulation?. In: Journal of Applied Physiology. 1994 ; Vol. 76, No. 2. pp. 893-901.
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