Erjefält I, Persson C G
AB Draco, Lund, Sweden.
Pulm Pharmacol. 1989;2(2):93-102. doi: 10.1016/0952-0600(89)90030-6.
Anaesthetised guinea-pigs received tracer macromolecules 70-340 kDa intravenously and their erythrocytes were labelled in vivo with 99mTc. Superfusion of tracheal mucosa (via oral catheter) with control solutions and inflammatory agents, was followed by sampling of tracheal surface liquids and tracheal tissue. Under baseline conditions no 125I-fibrinogen (340 kDa) and minimal amounts of erythrocytes, 131I-albumin (70 kDa), and FITC-D (150 kDa) were found in tracheal lavage fluids. Undisturbed baseline conditions with negligible leakage of plasma into airway tissue and lumen were thus obtained with the present provocation and sampling techniques. Superfusion during 2 min with bradykinin 2-10 nmol, histamine 2-8 nmol, capsaicin 0.1-0.4 nmol, PAF 4-8 nmol, ovalbumin 3-6 pmol (in sensitised animals) produced, within 1-10 min, a significant and dose-dependent accumulation of plasma in tracheal tissue and lavage fluids. PAF also induced a late phase plasma leakage response at 5 h. At 10 min PAF given intra-arterially produced a similar leakage into the tissue but less into the lumen compared to topical PAF. Intravenous PAF produced additional effects such as pulmonary oedema. Carbachol 8-16 nmol had only minimal effects on 'leakage' but produced severe bronchoconstriction. Toluene diisocyanate (0.003-0.03 microliter) produced dose-dependent and very sustained (17 h) plasma leakage. Recovery of plasma tracers in airway tissue and surface liquids, respectively, was significantly correlated. As examined with capsaicin, absorption of luminal macromolecules increased only slightly during the exudation process. It is suggested that the consistent inflammatory stimulus-induced passage of plasma into the lumen is a consequence of a load on the basal side of the epithelium induced by the extravasated plasma and its derived peptides. An increased interstitial pressure may transiently separate many epithelial cells allowing a mainly uni-directional almost unrestricted flow of large solutes into the lumen.
对麻醉的豚鼠静脉注射70 - 340 kDa的示踪大分子，并在体内用99mTc标记其红细胞。通过口腔导管用对照溶液和炎症介质对气管黏膜进行灌流，随后采集气管表面液体和气管组织样本。在基线条件下，气管灌洗液中未发现125I - 纤维蛋白原（340 kDa），红细胞、131I - 白蛋白（70 kDa）和FITC - D（150 kDa）的含量极少。因此，采用目前的激发和采样技术，可获得血浆向气道组织和管腔渗漏可忽略不计的未受干扰的基线条件。用2 - 10 nmol缓激肽、2 - 8 nmol组胺、0.1 - 0.4 nmol辣椒素、4 - 8 nmol血小板活化因子（PAF）、3 - 6 pmol卵清蛋白（在致敏动物中）进行2分钟灌流，在1 - 10分钟内，气管组织和灌洗液中的血浆出现显著的剂量依赖性积聚。PAF还在5小时时诱导了晚期血浆渗漏反应。在10分钟时，动脉内注射PAF与局部应用PAF相比，在组织中产生了类似的渗漏，但在管腔中的渗漏较少。静脉注射PAF产生了如肺水肿等额外效应。8 - 16 nmol卡巴胆碱对“渗漏”的影响极小，但产生了严重的支气管收缩。甲苯二异氰酸酯（0.003 - 0.03微升）产生剂量依赖性且非常持久（17小时）的血浆渗漏。气道组织和表面液体中血浆示踪剂的恢复显著相关。如用辣椒素检测，在渗出过程中管腔大分子的吸收仅略有增加。有人认为，持续的炎症刺激诱导血浆进入管腔是由于渗出的血浆及其衍生肽对上皮细胞基底侧造成负荷的结果。增加的间质压力可能会暂时分离许多上皮细胞，使大溶质主要单向且几乎不受限制地流入管腔。
