- 學位論文
H2O2刺激巨噬細胞移行和TNFα釋放機轉之探討
Mechanistic study of H2O2-stimulated macrophage migration and TNFα secretion
摘要
當病原菌入侵人體時，會刺激巨噬細胞釋出大量ROS參與免疫反應。本篇我們利用H2O2做為ROS的來源，研究其對巨噬細胞的影響。在RAW264.7巨噬細胞中，H2O2可誘發Src蛋白表現量增加。另外，以H2O2刺激老鼠的peritoneal macrophages（PEMs）；以及直接在老鼠腹腔打入H2O2所取出的巨噬細胞，二者的Src蛋白表現量皆明顯增加。此外，在in vivo中，經H2O2刺激後的巨噬細胞不但其細胞移行的能力上升且其TNFα的釋放顯著提高。進一步利用不同的抑制劑如PP2、PDTC來探討H2O2活化巨噬細胞的機轉時，我們發現NF-κB可能參與H2O2-mediated Src induction。令人感興趣的是，在巨噬細胞中大量存在的Src family kinases如Fgr、Lyn、Hck，其表現量並不會因為H2O2的刺激而有明顯的變化。這似乎暗示我們，Src在H2O2活化巨噬細胞過程中，扮演一個重要角色。
並列摘要
When humans are infected by pathogens, macrophages are activated and release large amounts of ROS to perform a variety of cellular functions in immune system. We use hydrogen peroxide for the source of ROS . In this study, we demonstrate the upregulation of Src in Raw264.7 and peritoneal macrophages (PEMs) by H2O2. And this H2O2–mediated Src induction is also observed in macrophages recovered from H2O2–challenged rats. Furthermore, for these macrophages, increased migration as well as TNFα secretion relative to control are also detected. Due to this H2O2-mediated Src induction could be inhibited by PP2 and PDTC, suggesting the participation of NF-κB in this signaling pathway. Interestingly, no significant alteration of the pt expression of Fgr、Lyn and Hck, the myeloid-specific Src family members, was observed, therefore these SFKs might not be the major players in H2O2-mediated signaling pathway. With these findings, we conclude that Src plays an important role in H2O2-induced macrophage activation.