鹼性磷酸酶對斑馬魚巨噬細胞發育及功能之影響

在人類中目前確認存在有四種Alkaline phosphatase(ALP)同功酶(isoenzyme)，分別為組織非專一性鹼性磷酸酶 (tissue nonspecific alkaline phosphatase, TNAP)、胎盤鹼性磷酸酶 (placental alkaline phosphatase, PLAP)、生殖細胞鹼性磷酸酶 (germ cell alkaline phosphatase, GCAP)和腸道鹼性磷酸酶 (intestinal alkaline phosphatase,IAP)，而TNAP不僅涉及礦化，也參與鈣化。先前之研究已確定zTNAP會參與斑馬魚之早期發育，尤其是在腎臟，此為斑馬魚後期造血的主要器官，在斑馬魚中腎臟調節紅血球、嗜中性白血球及巨噬細胞之發育。本研究之主要目的是為釐清zTNAP對於斑馬魚巨噬細胞發育及功能之影響。本實驗室先前注射zTNAP MO後與野生型斑馬魚比較發現，產生發育延遲、眼睛與卵黃延伸處變小及變短；本研究中利用斑馬魚MPO染色在尾部造血組織的嗜中性白血球數量明顯減少；斑馬魚中性紅染色視網膜及軀幹尾部的巨噬細胞數量明顯增加。本研究中指出當巨噬細胞缺乏鹼性磷酸酶時對於其趨化能力、吞噬能力及溶解能力都會下降；總而言之，鹼性磷酸酶對於斑馬魚巨噬細胞的發育及功能有著非常重要的作用。

There are four isozymes of alkaline phosphatase (ALP) in human, tissue nonspecific alkaline phosphatase (TNAP), placental alkaline phosphatase (PLAP), germ cell alkaline phosphatase (GCAP), and intestinal alkaline phosphatase (IAP). Recent studies showed that TNAP was not only involved in the mineralization, but also involved in calcification. Previous study showed that TNAP expressed at early development stages of zebrafish, especially at kidney, the adult organ for hematopoiesis that was similar to the bone marrow of mammals. In zebrafish, erythrocytes, macrophages and neutrophils generated the major regulation of kidney. The aims of study were to elucidate the effect of TNAP on zebrafish macrophage development and function. After TNAP morpholino injection, the zebrafish embryogenesis was delayed, the width and length of eyes and yolk extension were smaller and shorter than those of wild-type control, respectively. Using MPO stain, the number of neutrophils decreased in the caudal hematopoietic tissue (CHT). By neutral red staining, the number of macrophages increased in the retina and posterior trunk. In this study it induce macrophages function of migration, phagocytic and lysis decrease. In conclusion, ALP plays very important roles in macrophage development and function.