Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/15328
標題: 不同毒力之豬瘟病毒對於肺泡巨噬細胞及周邊血液淋巴細胞感染之細胞凋亡訊號表現
Expression of Apoptotic Signals Mediated by Different Virulent Classical Swine Fever Virus Infected Pulmonary Alveolar Macrophages and Peripheral Blood Lymphocytes
作者: 林家鈺
Lin, Chia-Yu
關鍵字: 豬瘟病毒
CSFV
肺泡巨噬細胞
細胞凋亡
PAM
apoptosis
出版社: 獸醫病理生物學研究所
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摘要: 豬瘟病毒在豬隻感染可造成免疫系統功能失調及呈現持續性感染現象,其分別與豬瘟病毒對淋巴細胞之傷害及與豬瘟病毒在網狀內皮系統之巨噬細胞的感染有著密切關聯。本實驗目的為探討豬瘟病毒感染肺泡巨噬細胞與淋巴細胞後的細胞凋亡(apoptotic)相關訊號表現,並比較不同毒力之豬瘟病毒在於訊號傳遞上是否有所差異,以期了解本病之致病機轉。本實驗中使用三株不同毒力之豬瘟病毒,包括無毒力的疫苗毒LPC病毒、與弱毒力的RL06-2病毒及強毒力的RL03-5病毒分別感染肺泡巨噬細胞及周邊血液淋巴細胞,並以流式細胞儀分析細胞之粒線體膜電位改變、細胞膜之完整性、pan-caspases活化情形,並使用西方墨點法偵測細胞之caspase-3活化與Akt磷酸化的程度。結果顯示,豬瘟病毒感染肺泡巨噬細胞後,僅RL03-5病毒感染後之細胞有較高細胞存活率,且發生apoptosis的比例較低,但在於粒線體膜電位改變與pan-caspases活化的程度相較於mock組而言,表現仍有增加,且具有顯著性差異(P < 0.01);以西方墨點法偵測結果顯示,豬瘟病毒感染肺泡巨噬細胞後可活化Akt及下游的GSK-3beta,且表現程度與病毒毒力呈現相關性(P < 0.05),而在細胞中caspase-3的表現則會受到豬瘟病毒的感染而降低。相對於豬瘟病毒感染淋巴細胞,除RL06-2感染淋巴細胞會造成pan-caspases活化的程度低於mock組外,其餘各種毒力之豬瘟病毒感染後,細胞存活率皆下降,apoptosis的比例增加,粒線體膜電位改變程度與pan-caspases活化的程度均增加;在西方墨點法偵測結果亦顯示豬瘟病毒感染淋巴細胞後可活化caspases-3。整體結果顯示,強毒豬瘟病毒RL03-5感染肺泡巨噬細胞雖仍會造成粒線體膜電位改變與pan-caspases活化程度增加,但其亦可強化anti-apoptotic protein phospho-Akt的表現,進而阻斷下游細胞凋亡作用蛋白之表現,造成細胞死亡率下降;而豬瘟病毒感染淋巴細胞後,可強化粒線體膜電位改變程度與pan-caspases的活化,導致淋巴細胞死亡,但其是否激活磷酸化Akt的表現,尚待進一步確認。
Infection of classical swine fever virus (CSFV) causes immunosuppression and virus persistence in swine, closely related to the injury of lymphocytes and persistent infection in macrophages. The aim of this study was to investigate the expression of apoptotic signals in pulmonary alveolar macrophages (PAMs) and peripheral blood lymphocytes (PBLs) after infected with different virulence of CSFV. Three different CSFV isolates including the avirulent LPC, low virulent RL06-2, and virulent RL03-5 were used in this study. The disruption of cellular mitochondrial membrane potential, cell membrane integrity, and activation of pan-caspases were analyzed by flow cytometry, and activation of caspase-3 and Akt were detected by Western blotting. The results show that the apoptotic signals of mitochondrial membrane potential disruption and pan-caspases activation were all increased in PAMs infected with CSFV, but the signal of cleaved caspase-3 was not significantly enhanced. In contrast, the anti-apoptotic signal of Akt phosphorylation and its down-stream GSK-3beta of CSFV-infected PAMs were also increased with virulence dependency. However, only RL03-5 infected PAMs had higher cell viability than mock infection and PAMs infected with LPC and RL06-2 CSFV. In contrast, besides RL06-2, increased mitochondrial membrane potential disruption, loss of cell membrane integrity, activation of caspases, and cell viability were less conspicuous in CSFV-infected PBLs than mock infection. Taken these results together, both CSFV infection in PAMs and PBLs initiated apoptotic signals, but the signals may be blocked in the down-stream of caspase effector proteins by the activation of anti-apoptotic signal of phospho-Akt in PAMs, leading to higher cell survival rate in virulent CSFV-infected PAMs. Whether CSFV induces activation of Akt in PBLs, need to be further elucidated.
URI: http://hdl.handle.net/11455/15328
其他識別: U0005-1208200820163200
文章連結: http://www.airitilibrary.com/Publication/alDetailedMesh1?DocID=U0005-1208200820163200
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