Regulation of biodefense system by neutrophil apoptosis

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Under steady-state conditions, the large daily production of neutrophils is balanced by their disappearance and apoptosis in the tissues without eliciting an inflammatory response. Normally, neutrophils disappear into the lung, oral cavity and gastrointestinal tract, where they may be lost from mucosal surfaces or die and become sequestered by macrophages. Infiltrated and activated neutrophils in periodontal tissues release enzymes, oxygen radicals, cytokines, and mediators of inflammation, and their persistent accumulation is associated with the destruction of tissue matrix or organ function, resulting in an exasperation of periodontal diseases. Thus, neutrophil elimination by apotosis is indeed a potentially injury-limiting cell disposal mechanism for the cessation of inflammation. In the present studies, we examined the mechanism of apoptosis of peripheral and oral neutrophils.When the nuclei from peripheral neutrophils were incubated with calcium and magnesium, internucleosomal DNA … More fragmentation was observed, but not in oral neutrophils. Peripheral neutrophil apoptosis was induced by actinomycin D and TNF-alpha, revealing internucleosomal DNA fragmentation, but oral neutrophils were resistant to the stimuli. When peripheral neutrophils were treated by TPA or FMLP which prime the cells, and cultured for an additional time, they underwent apoptosis with DNA fragmentation and did not become insensitive to apoptosis as oral neutrophils. Other signals which are aquired during migration to the oral cavity from the vessels may participate in the resistancy to apoptosis in oral neutrophils. A variety of modulators of intracellular signaling pathways, including protein kinase C and caspases, have been shown to participate in the regulation of neutrophil survival and apoptosis.However, H-7, an inhibitor of PKC,and AcY VADcmK,a caspase inhibitor, did not affect the DNA fragmentation in peripheral neutrophils.HL-60 cells which differentiate to granulocytes, underwent apoptosis by the inhibitor of proteasome which inhibited thymocytes apoptosis. It is difficult to measure neutrophil apoptosis quantitatively, therefor the apoptosis specific molecules such as Fas-FasL and Bcl-2 should be considered to elucidate the mechanism of neutrophil apoptosis.In the periodontal lesions, apoptosis of inflammatory cells including macrophages, neutrophils and lymphocytes is regulated by different mechanisms and modulates periodontitis. Less