Response of lung NK1.1-positive natural killer cells to experimental sepsis in mice.
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 were 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 postoperatively, 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 x 10(5)/lung compared with 2.97 +/- 0.27 x 10(5)/lung in the sham group), the peak of the CLP-induced ALI was associated with 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-gamma-positive cells decreased to 19.7 +/- 5.7% (P = 0.047), but TNF-alpha-positive cells grew to 26.7 +/- 3.3% (P = 0.02). In summary, severe CLP-induced dysfunction of lung NK1.1+CD-3 cells was demonstrated. This may influence the outcome of the animals during sepsis and acute lung damage.
Hirsh
Mark
M
Department of Surgery A and Laboratory for Shock and Trauma Research, Rambam Medical Center, Haifa, Israel. hirsh@tx.technion.ac.il
Kaplan
Viktoria
V
Dyugovskaya
Larissa
L
Krausz
Michael M
MM
D000818:Animals; D017209:Apoptosis; D001992:Bronchoalveolar Lavage Fluid; D004195:Disease Models, Animal; D005434:Flow Cytometry; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D008168:Lung / Q000276:immunology* / Q000473:pathology; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018805:Sepsis / Q000276:immunology* / Q000473:pathology