A 群鏈球菌可以引起多種嚴重程度不等的疾病，輕微如咽喉炎，嚴重之併發症，包括壞死性筋膜炎、敗血症、鏈球菌毒性休克症候群等。壞死性筋膜炎是A群鏈球菌感染嚴重的侵襲性症狀，快速導致肌肉快速崩解且造成的傷害是不可逆的，因此在感染初期的診斷就顯得更重要。在本研究中，我們透過臨床嚴重侵襲性病人組織檢體發現內皮細胞大量損傷以及發炎情況的增加，並觀察到A群鏈球菌在感染組織中大量存在並且與內皮細胞有共定位的現象。因此進而探討內皮細胞活化標誌血管生成素-1、-2以及多功能性蛋白kallistatin與臨床運用的生理參數相關性，血管生成素-2在感染前期與C-反應蛋白有顯著正相關；kallistatin在感染後期與血小板呈現顯著正相關、與C-反應蛋白有顯著負相關，說明這兩種蛋白質具在臨床上A群鏈球菌感染後的生物指標特性。我們也針對血管生成素系統在A群鏈球菌感染內皮細胞中扮演的角色去探討，細胞實驗中，感染長時間發現血管生成素系統失調現象，感染短時間發現血管生成素-2於細胞內減少以及細胞外顯著增加的現象，而我們推測血管生成素-2的釋放可能是藉由Weibel-Palade體路徑，並發現感染後短時間細胞滲透性就有顯著改變。綜合上述，我們推測嚴重A群鏈球菌感染下，血管生成素-2及kallistatin可作為預測A群鏈球菌感染後疾病走向的生物指標。雖然在A群鏈球菌感染內皮細胞所引起的血管生成素失調被觀察到，但短時間內皮細胞滲透性升高是否真的是藉由血管生成素失調所引起的還需要進一步去釐清。

Group A Streptococcus (GAS), Streptococcus pyogenes, can cause a wide spectrum of diseases ranging from mild pharyngitis to fatal complications such as necrotizing fasciitis, sepsis, streptococcal toxic shock syndrome. Necrotizing fasciitis is the most severe invasive disease in GAS infection. It was described as rapidly muscle destruction and irreversible damage, so the diagnosis at the beginning of infection is more important. In this study, we found a large number of endothelial cell damage and inflammatory response in invasive GAS patient‘s tissue sections. GAS was observed abundantly and co-localized with endothelial cells. Therefore, we investigated the correlation between endothelial cell activation markers angiopoietin-1, -2, multifunctional protein kallistatin and clinical parameters. Angiopoietin-2 was positively correlated with C-reactive protein in the acute phase while kallistatin was positively correlated with platelet, and negatively correlated with C-reactive protein in the late phase. The results indicated that the two proteins might have potential of biomarkers for GAS infection in clinical. We further investigated the role of the angiopoietin system in the GAS-infected endothelial cells. We demonstrated that the angiopoietin system dysregulation was observed after a long-term GAS infection in vitro. However, after a short-term GAS infection, the expression of intracellular Ang-2 decreased, but the concentration of Ang-2 in the GAS-infected endothelial cell culture medium increased. We speculated that the release of angiopoietin-2 may be induced through the Weibel-Palade bodies pathway. Significantly reduction of cell permeability in a short-term GAS infection was observed as well. Taken together, we demonstrated that angiopoietin-2 and kallistatin can be used as biomarkers for predicting the progression of GAS infection. Although angiopoietin dysregulation in GAS-infected endothelial cells is observed, it deserves further study to clarify whether the increase of permeability in endothelial cell is mediated by GAS-induced angiopoietin dysregulation.

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