Differential responses of the endothelial and epithelial barriers of the lung in sheep to Escherichia coli endotoxin.

Abstract

Although intravenous Escherichia coli endotoxin has been used extensively in experimental studies to increase lung endothelial permeability, the effect of E. coli endotoxin on lung epithelial permeability has not been well studied. To examine this issue in sheep, bidirectional movement ofprotein across the lung epithelial barrier was studied by labeling the vascular space with 13"I-albumin and-by instilling 3 ml/kg of an isosmolar protein solution with`-I-albumin into the alveoli. E. coli endotoxin was administered according to one of three protocols: intravenous alone (5-500 ug/kg), intravenous (5 pg/kg) plus low-dose alveolar endotoxin (10 pg/kg), and high-dose alveolar endotoxin alone (50-100 pg/kg). Alveolar liquid clearance was estimated based on the concentration of the instilled native protein.Sheep were studied for either 4 or 24 h. Although intravenous E. coli endotoxin produced a marked increase in transvascular protein flux and interstitial pulmonary edema, there was no effect on the clearance of either the vascular ("3'I-albumin) or the alveolar (1251-albumin) protein tracer across the epithelial barrier. High-dose alveolar E. coil endotoxin caused a 10-fold increase in the number of leukocytes, particularly neutrophils, that accumulated in the air spaces. In spite of the marked chemotactic effect of alveolar endotoxin, there was no change in the permeability of the epithelial barrier to the vascular or alveolar protein tracers. Also, alveolar epithelial liquid clearance was normal. Morphologic studies confirmed that the alveolar epithelial barrier was not injured by either intravenous or alveolar E. coli endotoxin. Thus, the alveolar epithelium in sheep is significantly more resistant than the lung endothelium to the injurious effects of E. coli endotoxin. (J. Clin. Invest. 1991. 88:864-875.) Key words: E. coli endotoxin * alveolar epithelium -lung endothelium * alveolar liquid clearance * acute lung injury

Bacterial-induced release of inflammatory mediators by bronchial epithelial cells

“…Overall, these findings are in accordance with the findings of WIENER-KORNISH et al [45], who have investigated the effect of E. coli endotoxin on sheep lung epithelium in vivo. These authors demonstrated that despite leading to a marked increase in interstitial pulmonary oedema and the number of neutrophils in the alveolar airspaces, E. coli endotoxin did not alter the alveolar epithelial permeability, as indicated by a lack of bidirectional movement of 125 I-labelled albumin across the alveolar epithelium.…”

Oxytocin-induced labor augments IL-1β-stimulated lung fluid absorption in fetal guinea pig lungs

“…The other four guinea pigs remained anesthetized until the 1-h experimental time had passed and were then killed, and samples were obtained. At this time, a blood sample was obtained for FD70 analysis, and the lungs were collected for determination of extravascular plasma equivalents as previously described (31,34,40,46). Trichloroacetic acid (TCA) precipitation of plasma and urine samples verified that the FITC label (Ͼ97%) remained bound to the dextran tracer throughout the experimental time period.…”

Elevation of KL-6, a lung epithelial cell marker, in plasma and epithelial lining fluid in acute respiratory distress syndrome

“…The significance of lung endothelial injury and increased permeability in ALI is well documented (6). Because an intact alveolar epithelial barrier is necessary to prevent alveolar flooding and facilitate recovery from acute respiratory distress syndrome (ARDS), lung epithelial integrity and function are important determinants of the clinical outcome in ALI (22,26,32). When alveolar type II cells are injured, normal alveolar epithelial fluid transport and removal of alveolar edema fluid are impaired (23).…”