Microscopy and Microanalysis

Biological Applications

Acute Lung Injury Induced by Staphylococcal enterotoxin B: Disruption of Terminal Vessels as a Mechanism of Induction of Vascular Leak

Ali Imran Saeeda1 p1, Sadiye Amcaoglu Riedera2 p2, Robert L. Pricea3, James Barkera1 p3, Prakash Nagarkattia2 and Mitzi Nagarkattia2 c1

a1 Division of Pulmonology, Department of Internal Medicine, University of South Carolina School of Medicine, Columbia, SC 29209, USA

a2 Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29209, USA

a3 Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC 29209, USA

Abstract

The current hypothesis of alveolar capillary membrane dysfunction fails to completely explain the severe and persistent leak of protein-rich fluid into the pulmonary interstitium, seen in the exudative phase of acute lung injury (ALI). The presence of intact red blood cells in the pulmonary interstitium may suggest mechanical failure of pulmonary arterioles and venules. These studies involved the pathological and ultrastructural evaluation of the pulmonary vasculature in Staphylococcal enterotoxin B (SEB)-induced ALI. Administration of SEB resulted in a significant increase in the protein concentration of bronchoalveolar lavage fluid and vascular leak in SEB-exposed mice compared to vehicle-treated mice. In vivo imaging of mice demonstrated the pulmonary edema and leakage in the lungs of SEB-administered mice. The histopathological studies showed intense clustering of inflammatory cells around the alveolar capillaries with subtle changes in architecture. Electron microscopy studies further confirmed the diffuse damage and disruption in the muscularis layer of the terminal vessels. Cell death in the endothelial cells of the terminal vessels was confirmed with TUNEL staining. In this study, we demonstrated that in addition to failure of the alveolar capillary membrane, disruption of the pulmonary arterioles and venules may explain the persistent and severe interstitial and alveolar edema.

(Received July 28 2011)

(Accepted January 24 2012)

Correspondence:

c1 Corresponding author. E-mail: Mitzi.Nagarkatti@uscmed.sc.edu

p1 Current address: Department of Pulmonary Critical Care and Sleep Medicine, MSC10-5550, University of New Mexico, Albuquerque, NM 87131, USA

p2 Current address: Laboratory of Immunology, Cellular Immunology Section, National Institutes of Health, Bethesda, MD 20892, USA

p3 Current address: Department of Pulmonary Critical Care and Sleep Medicine, Scott and White Health System, Texas A&M HCS, Temple, TX 76508, USA

Footnotes

† Authors contributed equally to this work.