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Granzyme K levels and NK cell lytic activity in experimental mice challenged with LPS and/or IL-2+IL-12

Abstract number: P763

Rucevic M., Fast L.D.

Objectives: Widespread activation of the innate immune system by infecting pathogens results in uncontrolled systemic release of an array of inflammatory mediators that generate clinical sepsis. Recently, we found that the levels of Granzyme K (GrK), a potent lymphocyte serine protease, correlate with the stage of sepsis but, the reason for increased GrK levels during inflammatory responses/sepsis is unclear. Since natural killer (NK) cells, which are know to be critically involved in the course of sepsis may also be responsible for the production of increased GrK levels, the aim of the present study was to investigate the changes in GrK levels along with the NK cells lytic activity in experimental animal models.

Methods: Recipients C57BL/6 mice were injected with bacterial lipopolysaccharide (LPS, 25 mg) in the first experimental model. In the second model, inflammatory response was induced in recipients by combined injection of cytokines, interleukin (IL)-2 and IL-12 (3×105 U rhuIL-2 + 1 mg rmuIL-12) which were also shown to be synergistic inducers of granzymes message. Our previously developed GrK-ELISA system was used to measure the plasma levels of GrK in LPS and/or IL-2+IL-12 injected recipients. Subsequently, the NK cells lytic activity was examined by testing the ability of single cell suspension prepared from recipient spleen cells to lyse the NK sensitive target, 51Cr-labeled YAC cells.

Results: Increase in GrK levels in mice plasma follow the increase in NK cell lytic activity in LPS challenged mice while in IL-2+IL-12 challenged mice no significant increase in NK cell lytic activity was observed. Furthermore, the changes in GrK levels in mice plasma of both experimental models were found to correlate with the changes in GrK levels of septic patients.

Conclusions: GrK could constitute at least one of the mechanisms by which NK cells contribute to systemic inflammation/sepsis. In addition, the results confirmed the role of GrK in sepsis pathology and further indicate that it may be a potential diagnostic marker and/or novel therapeutic target for further treatments of this life-threatening disease.

Session Details

Date: 19/04/2008
Time: 00:00-00:00
Session name: 18th European Congress of Clinical Microbiology and Infectious Diseases
Subject:
Location: Barcelona, Spain
Presentation type:
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