טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentCohen Victoria
SubjectResponse of Lung NK1.1-Positive Natural Killer Cells to
Experimental Sepsis in Mice
DepartmentDepartment of Medicine
Supervisors Professor Emeritus Michael Krausz
Dr. Mark Hirsh


Abstract

Natural killer cells (NKC) participate in the initiation of the immune response, and coordination between innate and adaptive immune mechanisms. Their role in systemic inflammation induced by trauma or infection (sepsis) is still controversial. In the present study, lung NKC and their response to experimental sepsis was investigated. Mice were subjected to cecal ligation and puncture (CLP) to induce sepsis and acute lung injury (ALI). Animals were sacrificed 1, 4, and 7 days post-operatively, and lung histopathology, pulmonary vascular permeability and inflammatory cells accumulation were assessed. On day 4, parameters of ALI were most prominent, and lung NK1.1+CD3¯ cells were isolated and studied by flow cytometry. Although CLP did not change the absolute number of lung NKC (2.47±0.52 ×105/lung compared with 2.97±0.27 x105/lung in the sham group), the peak of the CLP-induced ALI was associated with the severe dysfunction of lung NKC. Cell cytotoxicity decreased to 25.1±2.4% (p=0.002), and percentage of perforin-positive NKC to 2.7±0.5% (p=0.03). Cytokine profile of lung NK1.1+CD3¯ cells was prominently changed. The percentage of IFN-g-positive cells decreased to 19.7±5.7% (p=0.047), while TNF-a-positive cells grew to 26.7±3.3% (p=0.02). In summary, severe CLP-induced dysfunction of lung NK1.1+CD3¯ cells was demonstrated. This may influence the outcome of the animals during sepsis and acute lung damage.