HEPARIN PREVENTS ANTIGEN-INDUCED AIRWAY HYPERRESPONSIVENESS - INTERFERENCE WITH IP3-MEDIATED MAST-CELL DEGRANULATION

Heparin prevents antigen-induced airway hyperresponsiveness: interfere nce with IP3-mediated mast cell degranulation? J. Appl. Physiol. 76(2) : 893-901, 1994. - We hypothesized that heparin, because of its antial lergic and/or anti-inflammatory properties, modifies airway hyperrespo nsiveness (AHR). We studied the effects of inhaled heparin on AHR indu ced by specific antigen or by platelet-activating factor (PAF), a proi nflammatory mediator. Specific lung resistance (sRL) was measured in 1 7 allergic sheep before, immediately after, and serially for up to 2 h after airway challenge with either specific antigen or PAF. Airway re sponsiveness was expressed as the cumulative provocative dose of carba chol that increased sRL to 4 cmH(2)O/s [PD4, in breath units (BU; 1 BU = 1 breath of 1% carbachol solution)]. PD4 was determined on a baseli ne day and on various experimental days 2 h after airway challenge wit h antigen or PAF, without or after pretreatment with inhaled heparin ( 1,000 U/kg). Pretreatment with inhaled heparin prevented antigen-induc ed bronchoconstriction and postantigen AHR. PD4 was 26 +/- 2.6 (SE), 1 2 +/- 1.7, and 22 +/- 2.8 BU on baseline, antigen control, and posthep arin days, respectively. Heparin given immediately after the antigen c hallenge failed to modify the magnitude and/or duration of antigen-ind uced bronchoconstrictor response or postantigen AHR. Heparin also fail ed to prevent PAF-induced changes in sRL and AHR. In vitro heparin inh ibited anti-immunoglobin E- and 1,4,5-inositol triphosphate-mediated d egranulation of rat peritoneal mast cells without attenuating the effe cts 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.