Braley J F, Peterson L B, Dawson C A, Moore V L
J Clin Invest. 1979 Jun;63(6):1103-9. doi: 10.1172/JCI109402.
In previous studies with isolated perfused rabbit lungs, we observed that human serum albumin (HSA) and ovalbumin, introduced into the isolated lungs as an aerosol, entered the pulmonary circulation antigenically intact. The "inhaled" proteins were also broken down in the lung. When lungs from animals immunized with one protein inhaled the two proteins simultaneously, absorption of intact antigen was specifically reduced, and there was a nonspecific increase in the appearance of metabolites of both proteins in the blood. In the present study, we investigated the antigen-specific and nonspecific effects of two types of hypersensitivity responses on protein absorption across the air-blood barrier of isolated rabbit lungs. In one group of lungs, an acute hypersensitivity response was induced by introducing HSA into the blood perfusing lungs from HSA-immunized rabbits. In another, the rabbits had been previously exposed to chronic HSA aerosol until their lungs exhibited a chronic immunologic inflammatory response. Lungs from both groups were insufflated simultaneously with HSA, and a nonspecific protein, ovalbumin. Lungs in which the acute anaphylactic response was induced showed no alteration in the absorption of either intact protein compared with HSA-immunized controls, but absorbed a somewhat larger quantity of breakdown products of the specific antigen. Lungs undergoing the chronic alveolar inflammation were more permeable to nonspecific protein than were noninflamed lungs. Despite the increased permeability to nonspecific protein, the absorption of antigen was blocked as effectively as in immune but noninflamed controls. In these chronically inflamed lungs, the absorption of antigen breakdown products was enhanced. The results indicate that both immunologic and inflammatory mechanisms may control the amounts of inhaled soluble proteins that reach the blood via the alveolocapillary barrier. Alterations in the absorption of inhaled proteins and their metabolites across the air-blood barrier during certain types of hypersensitivity responses may be of immunologic and pathologic significance.
在之前对离体灌注兔肺的研究中，我们观察到，作为气雾剂引入离体肺的人血清白蛋白（HSA）和卵清蛋白，以抗原完整的形式进入肺循环。“吸入”的蛋白质在肺中也会被分解。当用一种蛋白质免疫的动物的肺同时吸入这两种蛋白质时，完整抗原的吸收会特异性降低，并且两种蛋白质代谢产物在血液中的出现会非特异性增加。在本研究中，我们调查了两种超敏反应对离体兔肺气-血屏障蛋白吸收的抗原特异性和非特异性影响。在一组肺中，通过将HSA引入灌注来自HSA免疫兔肺的血液中诱导急性超敏反应。在另一组中，兔子先前已暴露于慢性HSA气雾剂中，直到其肺部表现出慢性免疫炎症反应。两组的肺同时吹入HSA和一种非特异性蛋白质卵清蛋白。与HSA免疫的对照相比，诱导急性过敏反应的肺中两种完整蛋白质的吸收均未改变，但吸收了稍大量的特异性抗原分解产物。经历慢性肺泡炎症的肺对非特异性蛋白质的通透性比未发炎的肺更高。尽管对非特异性蛋白质的通透性增加，但抗原的吸收与免疫但未发炎的对照一样有效地被阻断。在这些慢性发炎的肺中，抗原分解产物的吸收增强。结果表明，免疫和炎症机制都可能控制通过肺泡毛细血管屏障到达血液的吸入可溶性蛋白质的量。在某些类型的超敏反应期间，吸入蛋白质及其代谢产物跨气-血屏障的吸收变化可能具有免疫和病理学意义。
