JF Pittet, JP Wiener-Kronish, V Serikov and MA Matthay
Cardiovascular Research Institute, University of California, San Francisco 94143.

Experimentally, the intravenous administration of a bolus dose of Escherichia coli endotoxin in sheep or a bolus dose of live Pseudomonas aeruginosa in rats is insufficient to cause injury to the alveolar epithelial barrier. Therefore, the first objective of these studies was to maximize the injury caused by live bacteria to the lung by administering a large dose of live P. aeruginosa into the lung perfusate of goat lungs in situ. P. aeruginosa (2.4 x 10(10) colony- forming units [cfu]) and [131I]albumin (vascular protein tracer) were added to the lung perfusate. Even though the bacterial inoculum remained very high in this isolated perfused lung system, there was no change in the permeability to protein or clearance of fluid across the alveolar epithelium, although there was an increase in lung endothelial protein permeability. Therefore, since systemic factors have been implicated in the severity and pathogenesis of septic lung injury, the second objective was to administer a continuous intravenous infusion of live P. aeruginosa over 8 h in intact anesthetized sheep. The eight sheep so treated exhibited an intact, functional alveolar barrier, even though there was an increase in lung endothelial permeability to protein and an increase in extravascular lung water. In fact, in these eight sheep, alveolar epithelial fluid transport was significantly greater than in control sheep. In the three other septic sheep there was injury to the alveolar epithelial barrier with an increase in permeability of the barrier to protein, an inability to transport fluid out of the airspaces, and an even greater increase in extravascular lung water.(ABSTRACT TRUNCATED AT 250 WORDS)

This article has been cited by other articles:

				J. M. Scarff and J. B. Goldberg Vaccination against Pseudomonas aeruginosa Pneumonia in Immunocompromised Mice Clin. Vaccine Immunol., February 1, 2008; 15(2): 367 - 375. [Abstract] [Full Text] [PDF]

				K.-J. Kim and A. B. Malik Protein transport across the lung epithelial barrier Am J Physiol Lung Cell Mol Physiol, February 1, 2003; 284(2): L247 - L259. [Abstract] [Full Text] [PDF]

				O. Lesur, C. Hermans, J.-F. Chalifour, J. Picotte, B. Levy, A. Bernard, and D. Lane Mechanical ventilation-induced pneumoprotein CC-16 vascular transfer in rats: effect of KGF pretreatment Am J Physiol Lung Cell Mol Physiol, February 1, 2003; 284(2): L410 - L419. [Abstract] [Full Text] [PDF]

				Y. Berthiaume, H. G. Folkesson, and M. A. Matthay Lung Edema Clearance: 20 Years of Progress: Invited Review: Alveolar edema fluid clearance in the injured lung J Appl Physiol, December 1, 2002; 93(6): 2207 - 2213. [Abstract] [Full Text] [PDF]

				C. Sartori and M.A. Matthay Alveolar epithelial fluid transport in acute lung injury: new insights Eur. Respir. J., November 1, 2002; 20(5): 1299 - 1313. [Abstract] [Full Text] [PDF]

				M. A. Matthay, H. G. Folkesson, and C. Clerici Lung Epithelial Fluid Transport and the Resolution of Pulmonary Edema Physiol Rev, July 1, 2002; 82(3): 569 - 600. [Abstract] [Full Text] [PDF]

				P. FACTOR, M. MENDEZ, G. M. MUTLU, and V. DUMASIUS Acute Hyperoxic Lung Injury Does Not Impede Adenoviral-mediated Alveolar Gene Transfer Am. J. Respir. Crit. Care Med., February 15, 2002; 165(4): 521 - 526. [Abstract] [Full Text] [PDF]

				J. J. Haddad, S. C. Land, W. O. Tarnow-Mordi, M. Zembala, D. Kowalczyk, and R. Lauterbach Immunopharmacological Potential of Selective Phosphodiesterase Inhibition. I. Differential Regulation of Lipopolysaccharide-Mediated Proinflammatory Cytokine (Interleukin-6 and Tumor Necrosis Factor-alpha ) Biosynthesis in Alveolar Epithelial Cells J. Pharmacol. Exp. Ther., February 1, 2002; 300(2): 559 - 566. [Abstract] [Full Text] [PDF]

				J. J. Haddad and S. C. Land Amiloride Blockades Lipopolysaccharide-Induced Proinflammatory Cytokine Biosynthesis in an Ikappa B-alpha /NF-kappa B-Dependent Mechanism . Evidence for the Amplification of an Antiinflammatory Pathway in the Alveolar Epithelium Am. J. Respir. Cell Mol. Biol., January 1, 2002; 26(1): 114 - 126. [Abstract] [Full Text] [PDF]

				L. B. WARE and M. A. MATTHAY Alveolar Fluid Clearance Is Impaired in the Majority of Patients with Acute Lung Injury and the Acute Respiratory Distress Syndrome Am. J. Respir. Crit. Care Med., May 1, 2001; 163(6): 1376 - 1383. [Abstract] [Full Text]

				N. Fukuda, H. G. Folkesson, and M. A. Matthay Relationship of interstitial fluid volume to alveolar fluid clearance in mice: ventilated vs. in situ studies J Appl Physiol, August 1, 2000; 89(2): 672 - 679. [Abstract] [Full Text] [PDF]

				J.-D. RICARD, L. MARTIN-LEFÈVRE, D. DREYFUSS, and G. SAUMON Alveolar Permeability and Liquid Absorption during Partial Liquid Ventilation of Rats with Perflubron Am. J. Respir. Crit. Care Med., January 1, 2000; 161(1): 44 - 49. [Abstract] [Full Text]

				M. LAFFON, J.-F. PITTET, K. MODELSKA, M. A. MATTHAY, and D. M. YOUNG Interleukin-8 Mediates Injury from Smoke Inhalation to both the Lung Endothelial and the Alveolar Epithelial Barriers in Rabbits Am. J. Respir. Crit. Care Med., November 1, 1999; 160(5): 1443 - 1449. [Abstract] [Full Text]

				K. MODELSKA, J.-F. PITTET, H. G. FOLKESSON, V. COURTNEY BROADDUS, and M. A. MATTHAY Acid-induced Lung Injury . Protective Effect of Anti-interleukin-8 Pretreatment on Alveolar Epithelial Barrier Function in Rabbits Am. J. Respir. Crit. Care Med., November 1, 1999; 160(5): 1450 - 1456. [Abstract] [Full Text]

				Y. Berthiaume, O. Lesur, and A. Dagenais Treatment of adult respiratory distress syndrome: plea for rescue therapy of the alveolar epithelium Thorax, February 1, 1999; 54(2): 150 - 160. [Full Text]

				J.-F. Pittet, I. Kudoh, and J. P. Wiener-Kronish Endothelial Exposure to Pseudomonas aeruginosa Proteases Increases the Vulnerability of the Alveolar Epithelium to a Second Injury Am. J. Respir. Cell Mol. Biol., January 1, 1998; 18(1): 129 - 135. [Abstract] [Full Text]

				J. M. Lasnier, O. D. Wangensteen, L. S. Schmitz, C. R. Gross, and D. H. Ingbar Terbutaline stimulates alveolar fluid resorption in hyperoxic lung injury J Appl Physiol, October 1, 1996; 81(4): 1723 - 1729. [Abstract] [Full Text] [PDF]