嗜中性白血球(neutrophils)在病菌入侵人體時會引發一連串的反應，呼吸爆發(respireatory burst)是嗜中性白血球徹底清除病菌的最後一個步驟。呼吸爆發發生在嗜中性白血球中的一個酵素系統—NADPH oxidese中。NADPH oxidase主要包含細胞膜嵌合蛋白質分子(gp91phox和p22phox)，以及位在細胞質內的蛋白質分子(p47phox, p67phox, p40phox)。活化態的NADPH oxidase會促使氧氣(O2)瞬間還原成超氧化物(superoxide, O2–)以及其他的各種具有毒性的ROS (reactive oxygen species)。許多研究指出，呼吸爆發過程中所產生的ROS除了具有清除病菌以及調控免疫反應的功能外，也有可以對鄰近的組織造成傷害。因此，過多或過少的ROS對於人體皆會造成傷害。嗜中性白血球具有多種不同的型態，priming是其中的一種，當嗜中性白血球處於這種狀態下，第二次的刺激物作用後會引發更大量的ROS產生。目前已經發現許多激素可以當作priming agent以使得嗜中性白血球處於此種priming的狀態下。假如我們將priming作用過程中的分子機制研究清楚，我們將可以用priming agent或是其抑制物還控制體內ROS的量。C-reactive protein (CRP)是一種急性期反應蛋白(acute-phase protein)，目前也已經發現它在ROS生成過程中扮演了一些角色。有些研究指出它會增加ROS的生成，但也有些研究持相反的意見。在本研究中，我們假設CRP是一個priming agent，並且試圖描繪出其中的分子機制，更進一步的想要瞭解為何CRP會同時具有增加和減少ROS生成的能力。首先，我們證實了CRP就像GM-CSF和LPS一般，的確具有priming的功效，並且與其他兩種priming agent相較之下，可以引發最大量的ROS產生，並且增加p47phox磷酸化的表現量，但細胞表面的cytochrome b558表現量並沒有因為受到CRP priming的作用而增加。而當CRP的濃度大於30μg/ml，原先會促進ROS生成的能力轉變成輕微的抑制ROS的產生，並且發現到p47phox磷酸化的表現量，和細胞表面的cytochrome b558表現量相較於低濃度的CRP也都有些微減少的情況。因此，我們證實了CRP會透過濃度的轉變，而造成在ROS生成的過程中扮演雙重的角色。透過這篇研究，我們證實了CRP在嗜中性白血球priming的過程中所扮演的角色和其分子機制。

Activated neutrophils respond to stimuli with a characteristic “respiratory burst” which is mediated by NADPH oxidase. NADPH oxidase consists of a membrane bound factors gp91phox, p22phox and the cytosol factors p47phox, p67phox, p40phox. The active NADPH oxidase triggers rapid reduction of oxygen to the superoxide anion (O2-) and other reactive oxygen species (ROS), which is so called respiratory burst. Numerous studies have demonstrated that ROS generated by NADPH oxidase not only kill invading pathogens and modulate immune response, but also damage the adjacent tissues. Therefore, the excess or deficiency of ROS is a danger in our bodies. Priming of ROS is an important phenotype of activated neutrophils. It is defined as enhancement of superoxide generation in response to a second activating stimulus. Many pro-inflammatory cytokines have been referred to as priming agents. If the molecular mechanisms of priming process are clearly defined, we will be able to use priming agents or their inhibitors to control the level of ROS. C-reactive protein (CRP), a membrane of acute-phase proteins, plays some roles on ROS production. Some studies have shown that it can enhance ROS production, but other studies showed it reduces ROS generation. In this study, we recognized CRP as a priming agent and investigated the molecular mechanisms of CRP priming. Furthermore, we tried to demonstrate how CRP enhances and reduces ROS production. At first, we confirmed that CRP, like GM-CSF and LPS, is a priming agent and it can enhance the highest ROS production after secondary stimulus. The p47phox phosphorylation increased in CRP-primed neutrophils, but the expression of cytochrome b558 on cell surface was not affected. We thus demonstrated that CRP primed neutrophils by the increased p47phox phosphorylation. When CRP was in a high concentration (more than 30μg/ml), the increased ROS production was converted to a slightly reduced level. The p47phox phosphorylation and the expression of cytochrome b558 on cell surface also had slightly decreased. Our results indicated that CRP had a concentration dependent dual effect on ROS productionon neutrophils. Through this study, we delineate the role and the molecular mechanism of CRP in the process of neutrophil priming.

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