| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Research Abstract |
Apoptotic CTLL-2 cells labelled with propidium iodide were intraperitoneally injected into mice, either C3H/HeJ (allogeneic) or C57BL/6 (syngeneic), which were pretreated with thioglycollate broth to induce sterile peritonitis. Peritoneal cells were then recovered from these mice at various times after injection, followed by flow cytometric analysis. Neutrophil number changed in a time-dependent manner up to 7 hours after injection, peaked at 5 hours. On the contrary, MIP-2 level in peritonium peaked 3 hours after injection. Apoptotic cells were phagocytosed mostly by macrophages, but not by neutrophils. Normal CTLL-2 cells induced a similar response to a lesser extent, whereas necrotic CTLL-2 cells obtained by three cycles of freezing and thawing induced a similar degree of neutrophil infiltration. When peritoneal macrophages were depleted from the mice by liposome-encapsulated dichloromethylene bisphosphonate, both neutrophil infiltration and MIP-2 production were suppressed, suggest
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ing that apoptotic cells injected peritoneally cause infiltration of neutrophils through phagocytosis of apoptotic cells by macrophages and subsequent production of MIP-2.
Whole-body X irradiation causes rapid and massive apoptosis in lymphoid tissues such as thymus. When B10 Thy 1.1 mice were irradiated with 4 Gy of X ray, thymocytes underwent apoptosis. In association with this, neutrophil number in the thymus increased transiently. infiltration of neutrophils was also confirmed histochemically. Some neutrophils appear to adhere to endothelial cells, while others appear to reside in thymic parencyma. Some macrophage-like cells appear to phagocytose apoptotic cells. In p53-/-mice both apoptosis and neutrophil infiltration were suppressed similarly after whole-body X-irradiation, suggesting that apotosis causes neutrophil infiltration. MIP-2 mRNA was detected 9 hours after irradiation, at which time the most significant number of neutrophils was infiltrated into the thymus. Taken together, massive apoptosis occurring rapidly in vivo causes transient infiltration of neutrophils. How apoptosis induces neutrophil infiltration and what roles neutrophils might have await further study. Less
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