Inflammatory passage of plasma macromolecules into airway wall and lumen

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.