Protektive Funktion von NK1.1⁺ Zellen in der murinen polymikrobiellen Peritonitis

Abstract

Abdominal sepsis due to anastomosis insufficiency after major abdominal surgery remains a life threatening condition. Interferon-gamma (IFNγ) is rapidly upregulated after inflammatory stimuli and is known to be a potent inducer of bactericidal effector mechanisms. Clinical as well as experimental data point to an essential protective role of IFNγ in the course of abdominal sepsis. The cellular source of IFNγ, especially at early stages of sepsis remains unclear. T cells can secrete substantial amounts of IFNγ but therefore require time for activation, maturation, and clonal proliferation. Thus, NK cells (or NKT cells) are better candidates for early IFNγ production in vivo. Our aim was to characterize the role of NK/NKT cells in murine experimental peritonitis. By injection with 200 μg αNK1.1 mAb (Hybridom PK136, ATCC) in 8 – 10 weeks old C57BL/6 mice 24 h prior to sepsis NK1.1⁺ cells (NK, NKT) were depleted. Sepsis was established by surgical insertion of a stent (size 18 gauge) in the ascending colon of experimental mice (CASP operation). Survival analysis and histochemistry were performed. αNK1.1 depleted animals revealed markedly increased susceptibility in the CASP model than controls (lethality 60% vs. 20% in controls) indicating a protective function of NK1.1⁺ cells in this model. Immunohistochemical analysis revealed a significant reduction of granulocytes and macrophages in livers from NK1.1 depleted animals 6 hand 12 h after surgery as compared to mice treated with control antibody. In conclusion, NK1.1⁺ cells play a crucial protective role in murine experimental peritonitis strongly suggesting an analogous function in human abdominal sepsis. Whether IFNγ mediates these effects remains to be elucidated.