Ahmed T, Syriste T, Mendelssohn R, Sorace D, Mansour E, Lansing M, Abraham W M, Robinson M J
Division of Pulmonary Disease, Mount Sinai Medical Center, Miami Beach, Florida 33140.
J Appl Physiol (1985). 1994 Feb;76(2):893-901. doi: 10.1152/jappl.1994.76.2.893.
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 days 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.
我们推测，肝素因其抗过敏和/或抗炎特性，可改变气道高反应性（AHR）。我们研究了吸入肝素对由特异性抗原或血小板活化因子（PAF，一种促炎介质）诱导的AHR的影响。在17只过敏绵羊气道用特异性抗原或PAF激发前、激发后即刻以及激发后连续2小时内测量特异性肺阻力（sRL）。气道反应性以将sRL增加至4 cmH₂O/s时的卡巴胆碱累积激发剂量[PD₄，以呼吸单位（BU；1 BU = 1次呼吸1%卡巴胆碱溶液）表示]来表示。在基线日以及在气道用抗原或PAF激发后2小时的不同实验日，在未用或吸入肝素（1000 U/kg）预处理的情况下测定PD₄。吸入肝素预处理可预防抗原诱导的支气管收缩和抗原激发后的AHR。在基线日、抗原对照日和肝素处理日后，PD₄分别为26±2.6（标准误）、12±1.7和22±2.8 BU。在抗原激发后立即给予肝素未能改变抗原诱导的支气管收缩反应的幅度和/或持续时间或抗原激发后的AHR。肝素也未能预防PAF诱导的sRL和AHR变化。体外实验中，肝素抑制抗免疫球蛋白E和1,4,5-肌醇三磷酸介导的大鼠腹膜肥大细胞脱颗粒，但不减弱Ca²⁺离子载体A-23187的作用。这些数据表明，在“急性反应者”中，肝素可能通过抑制1,4,5-肌醇三磷酸依赖性肥大细胞介质释放而非其抗炎作用来预防抗原诱导的支气管收缩和AHR。
