In vitro effect of recombinant human tumor necrosis factor-α on canine neutrophil apoptosis

Neutrophils (polymorphonuclear leukocytes: PMNs) are essential for the host defense against various infections and are often injurious to the host, causing inflammatory diseases where tumor necrosis factor-α (TNF-α) is suggested to play an important role. Since an effect of TNF-α on canine PMN apoptosis has not been studied, canine PMNs were stimulated with recombinant human (rh)TNF-α in the present study to investigate the effect of TNF-α on canine PMN apoptosis. PMN apoptosis and function to produce ROS were assessed by flow cytometry. Delayed apoptosis was observed in the PMNs treated with rhTNF-α at 100 ng/ml, accompanied by retention of capability to produce ROS. However, PMN apoptosis was accelerated by rhTNF-α combined with cycloheximide. Therefore, it is indicated that TNF-α is able to activate anti- and pro-apoptotic pathways in PMNs and that the inhibition of PMN apoptosis by TNF-α requires protein synthesis in the PMNs.