Bice D E, Williams A J, Muggenburg B A
Inhalation Toxicology Research Institute, Albuquerque, New Mexico 87185, USA.
Am J Respir Cell Mol Biol. 1996 Apr;14(4):341-7. doi: 10.1165/ajrcmb.14.4.8600938.
Lung transplant recipients can become asthmatic if they receive donor lungs from asthmatics. The maintenance of sensitivity in the lung allograft for inhaled allergens supports the concept that the mechanisms responsible for asthma are localized in the lungs, with a minimal systemic component. Pulmonary immunity to inhaled allergens is one mechanism which could be localized to the lung that would play a pivotal role in asthma. For example, the continued production of antibody to inhaled allergens in a human lung allograft could cause asthmatic responsiveness in the recipient. In this study, we tested the hypothesis that pulmonary immune cells continue to produce antibody in a canine allograft lung for relatively long times after transplantation. This was accomplished by immunizing four dogs by instillation of keyhole limpet hemocyanin (KLH) into a single lung lobe. After two challenges, the immunized lung from each dog was transplanted into a nonimmune recipient. Immune evaluations of recipients showed that anti-KLH antibody continued to be produced only in the donor lung for as long as 320 days after transplantation. Data from this study suggest that (1) immune cells in the lung can function independently from systemic immunity, (2) antibody production in the lung makes a significant contribution to blood antibody levels, and (3) immune cells in donor lungs can continue to produce antibody for relatively long times after transplantation. Therefore, immune cells in donor lungs from asthmatics could continue to produce antibody to allergens after transplantation, and this locally produced antibody may be responsible for the asthmatic responses observed in the recipients.
如果肺移植受者接受来自哮喘患者的供体肺,他们可能会患上哮喘。肺移植器官对吸入性过敏原保持敏感性,这支持了一种观点,即引发哮喘的机制定位于肺部,全身影响最小。对吸入性过敏原的肺部免疫是一种可能定位于肺部的机制,它在哮喘中起着关键作用。例如,人肺移植器官中持续产生针对吸入性过敏原的抗体可能会导致受者出现哮喘反应。在本研究中,我们测试了这样一个假设:在犬类同种异体移植肺中,肺免疫细胞在移植后相当长的时间内会持续产生抗体。通过将钥孔戚血蓝蛋白(KLH)滴注到单叶肺中对四只狗进行免疫来实现这一点。经过两次激发后,将每只狗的免疫肺移植到未免疫的受体中。对受体的免疫评估表明,移植后长达320天,仅在供体肺中持续产生抗KLH抗体。本研究的数据表明:(1)肺中的免疫细胞可以独立于全身免疫发挥作用;(2)肺中抗体的产生对血液抗体水平有显著贡献;(3)供体肺中的免疫细胞在移植后可以持续产生抗体达相当长的时间。因此,来自哮喘患者的供体肺中的免疫细胞在移植后可能会继续产生针对过敏原的抗体,而这种局部产生的抗体可能是导致受体出现哮喘反应的原因。