日本京都大学研究人员日前宣布，他们发现了脊椎动物血液循环开始的机制，即血液开始流动并非由于心脏搏动，而是一种酶像剪刀一样“切割”附着在血管内壁的红细胞，从而使血液开始流动。
京都大学生物学教授濑原淳子率领的研究小组利用斑马鱼的受精卵，在世界上首次拍摄到了红细胞开始循环时的情形。根据拍摄的图像，血管外生成的红细胞移动到血管内部，附着在血管内壁上。虽然心脏搏动已经开始，但是红细胞仍然停留在血管内壁超过一个小时，之后才一下子流动起来。
研究人员还发现，红细胞是依靠一种蛋白质附着在血管内壁上的。他们使分解这种蛋白质的酶“ADAM8”不再发挥作用，红细胞就一直停留在血管内。
由于这种酶也存在于人的血液细胞中，因此，研究人员认为，如果将来能够控制“ADAM8”的作用，或许可以预测并预防血栓的形成，进而帮助人们预防和治疗脑梗塞。
这一研究结果已刊登在新一期美国《当代生物学》杂志网络版上。
推荐原文出处：
Current Biology doi：10.1016/j.cub.2010.04.052
Metalloprotease-Dependent Onset of Blood Circulation in Zebrafish
Atsuo Iida, Kazuya Sakaguchi, Kiyoaki Sato, Hidetoshi Sakurai, Daigo Nishimura, Aya Iwaki, Miki Takeuchi, Makoto Kobayashi, Kazuyo Misaki, Shigenobu Yonemura, Atsuo Kawahara, Atsuko Sehara-Fujisawa
The primitive blood circulation requires intravascular plasma flow [1]. However, it remains unclear whether the onset of earliest blood circulation is dependent solely on establishment of a functional circulatory organ or whether it also requires active processes inherent in blood cells. In this study, we present novel mechanisms for the onset of blood circulation by monitoring fluorescently labeled blood precursors and blood vessels in zebrafish. The earliest blood circulation occurs synchronously. This synchrony is achieved by the retention of erythroid precursors on the lumen of the vasculature after their invasion from the subaortic region, and then by simultaneous release of these precursors into the flow. Morphological and biochemical analyses suggest that the onset of blood circulation accompanies disruption of blood cell-to-vessel adhesion and requires metalloprotease-dependent processes. ADAM8, a member of the a disintegrin and metalloprotease (ADAM) family, mediates the onset of blood circulation. In ADAM8-depleted embryos, erythroid cells fail to detach from the vascular lumen and stagnate. Expression of a protease-defective ADAM8 in erythroid cells causes dominant-negative effects on blood circulation, suggesting cell-autonomous roles of ADAM8. Based on these findings, we propose that the first erythroid cells require both flow-dependent passive and proteolysis-dependent active processes to enter the circulation.
