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Original Articles
Apoptosis of Peripheral Blood Cells Stimulated by Lipopolysaccharide, Cytokines, or Escherichia coli
Jung Hyun Choi/Wan Shik Shin/Hee Jung Kim/Dong Ho Huh
Department of Internal Medicine, St Mary's Hospital, Catholic University of Korea, Seoul, Korea. Department of Clinical Research Institute, St Mary's Hospital, Catholic University of Korea, Seoul, Korea.
Vol.31 Num.4 (p279~290)
Introduction and Methods : Apoptosis is a natural suicidal mechanism of eukaryotic cells to maintain the homeostasis of hosts. It comprises important pathogenesis of autoimmune diseases, cancers, and some infectious diseases. To access the role of apoptosis in the pathogenesis of infectious diseases, we studied the difference in apoptotic patterns of polymorphonuclear leukocytes and of monocytes to various stimuli, such as lipolysaccharide (LPS), tumor necrosis factor (TNF)-α, interleukin (IL)-6, granulocyte, macrophage-colony stimulating factor (GM-CSF), or Escherichia coli (E. coli). The cell survival and expression of Fas and Fas ligand(FasL), bcl-2, and IL-lβ converting enzyme (ICE) were evaluated by flow cytometry, northern blotting or wastern blotting analysis.

Results : The survival of polymorphonuclear leukocytes and monocytes was prolonged after stimulation with LPS and cytokines. Stimulation of Fas with Fas monoclonal antibody induced apoptosis in both polymorphonuclear leukocytes and monocytes. Expressions of Fas and FasL were more dominant in polymorphonuclear leukocytes than in monocytes. bcl-2 was expressed only in monocytes and was associated with the delay of apoptosis. ICE is a common pathway to apoptosis and thus pretreatment with ICE inhibitor could partially inhibit the apoptosis in both cells. Interestingly, E. coli prolonged the life-span of polymorphonuclear leukocytes but accelerated apoptosis in monocytes in spite of the over-expression of bcl-2.

Conclusion : Polymorphonuclear leukocytes and monocytes might have different apoptotic mechanisms to maintain their homeostasis. Polymorphonuclear leukocytes have only one mechanism to apoptosis, namely via Fas-FasL, whereas, monocytes have both Fas-FasL and bcl-2 mechanisms. These differences may be associated with their primary functions and natural life-span. Direct stimulation by live E. coli accelerated apoptosis in monocytes in spite of the over-expression of inhibitor of apoptosis, i.e. bcl-2. It could be due to activation of other apoptotic mechanisms by 2. coli, which may detour the anti- apoptotic action of bcl-2 or direct inhibition of bcl-2 function.
Keywords : Apoptosis, Polymorphonuclear leukocytes, Monocytes, Cytokine