Wohlsen A, Martin C, Vollmer E, Branscheid D, Magnussen H, Becker W M, Lepp U, Uhlig S
Research Centre Borstel, Borstel, Germany.
Eur Respir J. 2003 Jun;21(6):1024-32. doi: 10.1183/09031936.03.00027502.
To study the role of small airways in the early allergic response (EAR), the method of human precision-cut lung slices (PCLS) was developed and used to examine the bronchoconstriction elicited by passive sensitisation and allergen provocation. Viable human PCLS of 250-microm thickness containing airways <1.5 mm in outer diameter were prepared from lung lobes obtained from lung resection and taken into culture. According to the low release of lactate dehydrogenase and the constant ciliary beat frequency, human PCLS were viable for at least 3 days. Following overnight passive sensitisation with serum from allergic individuals, administration of grass-pollen extract or activating immunoglobulin E antibody resulted in immediate airway contraction that was quantified by videomicroscopy. The extent of the EAR increased with decreasing airway size (outer airway diameter), with the strongest response occurring in the terminal bronchioles. Histamine receptor antagonism was ineffective, and leukotriene or thromboxane receptor antagonism attenuated the early allergic response only in some cases. However, simultaneous blockade of leukotriene and thromboxane receptors almost completely prevented the early allergic response in the precision-cut lung slices from all individuals, suggesting such a dual treatment as a potential future asthma therapy.
为研究小气道在早期过敏反应（EAR）中的作用，开发了人类精密切割肺切片（PCLS）方法，并用于检测被动致敏和过敏原激发所引发的支气管收缩。从肺切除获得的肺叶制备出外径<1.5 mm气道的250微米厚的活性人类PCLS，并进行培养。根据乳酸脱氢酶的低释放和恒定的纤毛摆动频率，人类PCLS至少存活3天。用过敏个体的血清进行过夜被动致敏后，给予草花粉提取物或激活免疫球蛋白E抗体可导致即刻气道收缩，通过视频显微镜进行定量。EAR的程度随着气道尺寸（气道外径）的减小而增加，最强反应发生在终末细支气管。组胺受体拮抗无效，白三烯或血栓素受体拮抗仅在某些情况下减弱早期过敏反应。然而，同时阻断白三烯和血栓素受体几乎完全阻止了所有个体精密切割肺切片中的早期过敏反应，表明这种双重治疗作为未来潜在的哮喘治疗方法。
