活性氧化物調控九孔(Haliotis diversicolor) 血球細胞
之細胞遷移作用

在無脊椎動物中，血液細胞的遷移已經知道會參與在幾個重要的生理功能之中，特別是在防禦時的細胞吞噬或傷口修復過程中的血栓形成及免疫調控等，然而，無脊椎動物細胞遷移過程中的細胞趨化現象跟詳細的調控機制都尚未清楚。在近期的研究中指出，活性氧化物(Reactive oxgen species, ROS)雖會對細胞造成危害，但同時也參與並調控了細胞多種的生理反應。在哺乳動物細胞中，ROS會直接調控癌細胞、神經細胞及內皮細胞等細胞遷移行為，ROS也會調控在斑馬魚傷口周圍免疫細胞的趨化，因此，ROS可能也會參與調控無脊椎動物血球細胞之細胞遷移。本研究發現九孔體內的CD3+血球細胞會表現較高量的ROS，移動速度較快，但移動方向較隨機; 而九孔的類巨嗜細胞則表現較低量的ROS，雖然移動速度較慢，但移動較具方向性。當經由diphenyleneiodonium chloride (DPI)抑制ROS表現時，只有CD3+血球細胞的移動能力受到顯著的抑制，同時也會影響血球細胞之移動分佈。標定細胞製造ROS的NADPH氧化酶，發現氧化酶會集中在CD3+血球細胞的絲狀偽足反側；而在類巨嗜細胞中，NADPH氧化酶則是以點狀分佈在細胞裡。在經由Wortmannin及LY294002抑制血球細胞的PI3K訊息傳遞後，細胞擴散分布及ROS表現都受到明顯的抑制，類似於使用抑制劑降低ROS表現的效用，指出PI3K訊息傳遞與細胞內ROS產生有關。故此，我推論ROS在九孔血球的細胞遷移過程中會經由NADPH氧化酶生成，而主要調控血球細胞內的actin的解構作用，並且經由PI3K訊息傳遞調控。

關鍵字

九孔；活性氧化物；血球細胞；細胞遷移

並列摘要

Hemocyte migration in invertebrates has been known to be involved in several important physiological functions such as phagocytosis and wound healing. In addition to chemotaxis or haptotaxis, the regulatory mechanisms on the cell migration are still needed to be clearly unraveled. In recent studies, reactive oxygen species (ROS) are not only generally considered as threat for cells, but also found as important modulators for some cell behaviors. In mammals, ROS can activate migration in different types of cells including neurons, endothelial cells, and cancer cells. ROS also serves as chemoattractants and stimulators for leukocytes in zebra fish. Therefore, ROS may also play crucial roles in invertebrate hemocyte migration. In abalone, CD3+ hemocytes perform high ROS production and active cell mobility with random migrating directions, whereas marcophage-like hemocytes are totally different. The results showed that inhibition of ROS production by diphenyleneiodonium chloride (DPI) significantly reduced CD3+ hemocytes mobility, and also affected the spreading of hemocyte monolayer. NADPH oxidase, the main producer of cellular ROS, was apparently located at the opposite site of the filopodia in the migrating CD3+ hemocyte, but distributed as dot pattern in macrophage-like hemocyte. The spreading of cell-layer and production of ROS were both significantly inhibited by PI3K pathway inhibitors, woermannin or LY294002. Due to the effects of depressing PI3K were similar to suppress the production of cellular ROS, these data inferred that PI3K pathway may regulate ROS generation. Therefore, it was suggested that ROS generated by NADPH oxidase should mediate in actin filament assembling during cell migration under the regulation of PI3K pathway in abalone hemocytes.

並列關鍵字

abalone ； ROS ； hemocyte ； cell migration

參考文獻

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活性氧化物調控九孔(Haliotis diversicolor) 血球細胞之細胞遷移作用

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