Adamiak Mateusz, Ratajczak Mariusz Z
Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, 500 S. Floyd Street, Rm. 107, Louisville, KY 40202 USA.
Department of Regenerative Medicine, Warsaw Medical University, Warsaw, Poland.
Curr Stem Cell Rep. 2017;3(3):172-180. doi: 10.1007/s40778-017-0087-3. Epub 2017 Jul 10.
Several mechanisms have been postulated to orchestrate mobilization of hematopoietic stem/progenitor cells (HSPCs), and still more work is needed to better understand this process and to gain better mechanistic insight.
Evidence accumulated that mobilization of HSPCs is a part of innate immunity response to tissue organ injury, stress, and infection. This evolutionary ancient process is orchestrated by granulocytes and monocytes that trigger activation of complement cascade and the coagulation cascade.
We will present data from our laboratory that initiation of complement cascade activation and subsequently activation of the coagulation cascade during mobilization process are dependent on mannan-binding lectin (MBL). The mannan-binding pathway activates MBL-associated serine proteases (MASP-1 and MASP-2) that cleave the third complement component C3 and prothrombin. Cleavage of C3 leads to formation of classical C5 convertase and cleavage of prothrombin generates thrombin, which has "C5-like convertase" activity. Finally, both C5 convertase and thrombin cleave the fifth complement component C5, and activate distal part of the complement cascade that is crucial for egress of HSCPs from bone marrow niches into peripheral blood.
已经提出了几种机制来协调造血干/祖细胞（HSPCs）的动员，仍需要更多的研究来更好地理解这一过程并获得更深入的机制见解。
积累的证据表明，HSPCs的动员是对组织器官损伤、应激和感染的固有免疫反应的一部分。这个进化上古老的过程由粒细胞和单核细胞协调，它们触发补体级联反应和凝血级联反应的激活。
我们将展示来自我们实验室的数据，即在动员过程中补体级联反应的启动以及随后凝血级联反应的激活依赖于甘露糖结合凝集素（MBL）。甘露糖结合途径激活MBL相关丝氨酸蛋白酶（MASP-1和MASP-2），它们切割第三补体成分C3和凝血酶原。C3的切割导致经典C5转化酶的形成，凝血酶原的切割产生凝血酶，其具有“C5样转化酶”活性。最后，C5转化酶和凝血酶都切割第五补体成分C5，并激活补体级联反应的远端部分，这对于HSCPs从骨髓龛进入外周血至关重要。
