Hayes J P, Kuo H P, Rohde J A, Newman Taylor A J, Barnes P J, Chung K F, Rogers D F
Department of Thoracic Medicine, National Heart & Lung Institute, London, UK.
Eur J Pharmacol. 1995 Jan 13;292(2):127-34. doi: 10.1016/0926-6917(95)90004-7.
Trimellitic anhydride is a cause of occupational asthma in humans. We have previously found that tracheal instillation of trimellitic anhydride conjugated to guinea pig serum albumin induces acute bronchoconstriction and airway plasma exudation in sensitised animals, responses mediated primarily via histamine release. In the present study, neural mechanisms mediating bronchoconstriction and goblet cell secretion were determined in trimellitic anhydride-sensitised guinea pigs using the ganglionic blocker hexamethonium to eliminate efferent reflex mechanisms, pretreatment with capsaicin to eliminate afferent mechanisms, or cimetidine and mepyramine to eliminate histamine-mediated mechanisms. The magnitude of secretion of intracellular mucus from tracheal goblet cells was quantified morphometrically as a mucus score which is inversely related to the degree of discharge. Guinea pigs were injected intradermally either with 0.1 ml 0.3% trimellitic anhydride in corn oil or with corn oil alone as control. Fourteen to eighteen days later all sensitised animals had developed specific immunoglobulin (Ig) G1 antibodies whereas the controls had not. Tracheal instillation of conjugated trimellitic anhydride in anaesthetised animals significantly increased airway lung resistance (RL) 24-fold in sensitised guinea pigs (34.3 +/- 7.9 cm H2O.ml-1.s) compared with controls (1.4 +/- 0.1 cm H2O.ml-1.s). Mucus score was significantly reduced by 51% (indicating goblet cell secretion) in sensitised guinea pigs (183 +/- 22 mucus score units) compared with controls (372 +/- 41 mucus score units). The antihistamines significantly inhibited conjugated trimellitic anhydride-induced bronchoconstriction by 89%, but did not significantly affect goblet cell discharge. Hexamethonium alone did not significantly affect conjugated trimellitic anhydride-induced bronchoconstriction or goblet cell secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
偏苯三酸酐是人类职业性哮喘的一个病因。我们之前发现，将与豚鼠血清白蛋白结合的偏苯三酸酐经气管内注入可在致敏动物中诱发急性支气管收缩和气道血浆渗出，这些反应主要通过组胺释放介导。在本研究中，我们使用神经节阻滞剂六甲铵来消除传出反射机制、用辣椒素预处理来消除传入机制，或用西咪替丁和甲氧苄胺来消除组胺介导的机制，从而确定在偏苯三酸酐致敏的豚鼠中介导支气管收缩和杯状细胞分泌的神经机制。通过形态计量学将气管杯状细胞的细胞内黏液分泌量量化为黏液评分，该评分与排出程度呈负相关。给豚鼠皮内注射0.1 ml玉米油中的0.3%偏苯三酸酐或仅注射玉米油作为对照。14至18天后，所有致敏动物都产生了特异性免疫球蛋白（Ig）G1抗体，而对照组则没有。与对照组（1.4±0.1 cm H₂O·ml⁻¹·s）相比，在麻醉动物中经气管注入结合的偏苯三酸酐后，致敏豚鼠的气道肺阻力（RL）显著增加了24倍（34.3±7.9 cm H₂O·ml⁻¹·s）。与对照组（372±41黏液评分单位）相比，致敏豚鼠的黏液评分显著降低了51%（表明杯状细胞分泌）（183±22黏液评分单位）。抗组胺药显著抑制结合的偏苯三酸酐诱导的支气管收缩达89%，但对杯状细胞排出没有显著影响。单独使用六甲铵对结合的偏苯三酸酐诱导的支气管收缩或杯状细胞分泌没有显著影响。（摘要截选至250字）
