Lung to blood passage of different-sized molecules during lung inflammation in the rat

Abstract

The passage of different-sized marker molecules over the lower respiratory tract into the blood circulation during pulmonary inflammation induced by dextran, endotoxin [i.e., lipopolysaccharide from Escherichia coli (LPS)], or ferritin was assessed in the rat. Bovine immunoglobulin G (BIgG, mol wt = 150,000 Da), bovine serum albumin (BSA, mol wt = 67,000 Da), and the nonapeptide 1-deaminocysteine-8-D-arginine vasopressin (dDAVP, mol wt = 1,067 Da) were used as permeability markers after intratracheal instillation. The pathophysiological indexes of a proceeding lung inflammation were increased total cell number, changed leukocyte proportions and increased total protein content obtained in bronchoalveolar lavage, and lung edema formation shown as an increased lung wet-dry weight difference. Intratracheal instillation of dextran induced a moderate neutrophil invasion into the lungs but had no effect on the passage of the different markers over the lungs (BIgG 1.8 +/- 0.6%, BSA 3.5 +/- 1.2%, dDAVP 26.1 +/- 20.7%) compared with control rats instilled with the markers alone (1.8 +/- 0.4%, 4.1 +/- 1.3%, 20.0 +/- 3.8%, respectively). Endotoxin administration resulted in markedly higher lavage cell counts and lung edema concomitantly with an increased lung passage of the markers (3.2 +/- 0.9%, 22.0 +/- 6.1%, 33.3 +/- 12.0%, respectively; P less than 0.01-P less than 0.001). The highest marker passage was obtained when the inflammation was most severe, i.e., after ferritin administration (17.6 +/- 2.3%, 60.0 +/- 6.7%, 41.6 +/- 6.9%, respectively; P less than 0.001), which resulted in markedly elevated lavage cell numbers and protein content as well as edema formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Protein transport across the lung epithelial barrier

“…With severe inflammation following the use of large concentrations of ferritin, bIgG clearance approached the clearance of the two smaller tracers (43). These reports are consistent with the hypothesis that clearance of BSA and bIgG via the paracellular pathways of the respiratory epithelial Question marks next to the receptors or processes denote the insufficient proof of receptor expression or existence of such processes in type II cells.…”

“…A later study on alveolar epithelial permeabilities of urea, sucrose, inulin, and dextran (60-90-kDa range) in saline-filled dog lungs also showed a similar relation between the size of molecules and permeabilities (113). In support of these findings, a larger permeability-surface area product for sucrose than for albumin in rabbit lungs was reported (120), and the bioavailability of intratracheally instilled proteins exhibited lower values for larger proteins (42,43). Analysis of the amount of radiolabeled proteins that remained in the human lung 8 h after intratracheal instillation indicated that larger proteins cleared at a slower rate than smaller proteins (52).…”

“…Similarly, intratracheal instillation of a low dose of E. coli endotoxin resulted in neutrophil recruitment into air spaces of sheep lungs without a significant change in fluxes of labeled protein across the air-blood barrier in either air space-to-vascular or opposite direction (121). After challenge of lungs with large amounts of inflammatory agents, lung protein permeability increased secondary to generation of free radicals and other reactive metabolites released by inflammatory cells, but not by the recruited inflammatory cells per se (43). Intratracheal instillation of ferritin resulted in neutrophil recruitment with a large increase in lung protein clearance, whereas coadministration with a hydroxyl radical scavenger, mannitol, abrogated the increase in passage of protein markers into vascular space from the air spaces (43).…”

“…Pulmonary inflammation induced by intratracheal instillation of Escherichia coli endotoxin or ferritin in rat lungs caused dose-dependent increases in the lung clearance of bovine IgG (bIgG), BSA, and DDAVP such that the changes in lung clearance of these markers were greater for bIgG and BSA than for DDAVP (43). With severe inflammation following the use of large concentrations of ferritin, bIgG clearance approached the clearance of the two smaller tracers (43).…”

Pneumoproteinaemia: a new perspective in the assessment of lung disorders

“…Whether a loss of the charge-selectivity is also present and exacerbates this oedematous process remains to be established but this is quite conceivable by analogy with the glomerular barrier. Experimental studies have shown that the passage of different-sized marker molecules from the lower respiratory tract into the bloodstream also increases during inflammatory conditions and correlates with the severity of the lung injury [9,10]. The main route of clearance for lung proteins leaking into the interstitial space is via the bloodstream; lymphatic drainage accounting for about 25% [4].…”