Date of Award

1-1-2011

Document Type

Campus Access Dissertation

Department

Biomedical Science

First Advisor

Mitzi Nagarkatti

Second Advisor

Prakash Nagarkatti

Abstract

Acute lung injury (ALI) remains as an important health condition in intensive care units all over the world, with approximately 200,000 cases per year in the United States only. ALI can develop as a medical complication following inhalation of a toxic substance, septic shock, blood transfusions and pneumonia. The treatment options are based on supportive care, and the mortality rates fluctuate between 35 and 60%, based on the age of patients. The role of activated T cells and failure in capillaries of the lungs has been demonstrated in ALI; however the detailed mechanism of disease remains unclear. This study offers a better understanding of the mechanism of Staphylococcal Enterotoxin B (SEB)-induced acute lung injury. More specifically, we demonstrate that iNK T cells, which previously were shown to be only stimulated by glycolipids, can also get activated by a protein antigen, SEB; therefore directly contributing to severe respiratory failure. In addition, we show that upon SEB inhalation, not only the capillaries but also the terminal vessels of the lungs undergo mechanical failure, thereby contributing to edema. We also demonstrate the differential regulation of miRNAs in SEB-induced ALI, and identify two different miRNAs (miRNA155 and miRNA182), which play important roles in SEB-induced proliferation. Finally, we demonstrate the therapeutic effectiveness of resveratrol, a natural plant product, in SEB-induced acute lung injury. These studies provide novel mechanistic information about Acute Lung Injury, and also present an alternate natural treatment modality.

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