Serine protease inhibitors serpina1 and serpina3 are down-regulated in bone marrow during hematopoietic progenitor mobilization.
Serine protease inhibitors serpina1 and serpina3 are down-regulated in bone marrow during hematopoietic progenitor mobilization.
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DOI：
10.1084/jem.20042299
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发表时间：
2005-04-04
期刊：
影响因子：
--
通讯作者：
Lévesque JP
中科院分区：
文献类型：
--
作者：
Winkler IG;Hendy J;Coughlin P;Horvath A;Lévesque JP
动员造血祖细胞进入血液涉及到骨髓中大量释放中性粒细胞丝氨酸蛋白酶。我们推测，这些中性粒细胞丝氨酸蛋白酶的活性受骨髓局部产生的天然抑制物(SERPINA1和SERPINA3)的表达调节。我们发现SERPINA1和Serpina3在骨髓中被许多不同的造血细胞群体转录，在粒细胞集落刺激因子或化疗诱导的动员过程中，SERPINA1和Serpina3在蛋白质和mRNA水平上都发生了强烈的下降。由于SERPINA1在肝脏中的表达保持不变，导致动员过程中血浆浓度没有变化，这种降低的表达仅限于骨髓。在动员过程中SERPINA1和SERPINA 3的下调可能导致丝氨酸蛋白酶及其抑制物之间的平衡改变，并在骨髓血管外液中积聚活性的中性粒细胞丝氨酸蛋白酶，这些酶裂解和失活对骨髓内造血祖细胞的保留至关重要的分子。这些数据表明，SERPINA1和Serpina3在调节骨髓造血微环境以及影响造血祖细胞的迁移行为方面发挥了意想不到的作用。
Mobilization of hematopoietic progenitor cells into the blood involves a massive release of neutrophil serine proteases in the bone marrow. We hypothesize that the activity of these neutrophil serine proteases is regulated by the expression of naturally occurring inhibitors (serpina1 and serpina3) produced locally within the bone marrow. We found that serpina1 and serpina3 were transcribed in the bone marrow by many different hematopoietic cell populations and that a strong reduction in expression occurred both at the protein and mRNA levels during mobilization induced by granulocyte colony-stimulating factor or chemotherapy. This decreased expression was restricted to the bone marrow as serpina1 expression was maintained in the liver, leading to no change in plasma concentrations during mobilization. The down-regulation of serpina1 and serpina3 during mobilization may contribute to a shift in the balance between serine proteases and their inhibitors, and an accumulation of active neutrophil serine proteases in bone marrow extravascular fluids that cleave and inactivate molecules essential to the retention of hematopoietic progenitor cells within the bone marrow. These data suggest an unexpected role for serpina1 and serpina3 in regulating the bone marrow hematopoietic microenvironment as well as influencing the migratory behavior of hematopoietic precursors.
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DOI：
10.1164/ajrccm.157.1.9702033
发表时间：
1998-01-01
影响因子：
24.7
作者：
Knoell, DL;Ralston, DR;Wewers, MD
通讯作者：
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影响因子：
5.5
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Cowland, JB;Borregaard, N
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影响因子：
20.3
作者：
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通讯作者：
Moore, MAS
影响因子：
6.5
作者：
de Haan, G;Ausema, A;Dontje, B
通讯作者：
Dontje, B
DOI：
10.1073/pnas.88.21.9417
发表时间：
1991-11-01
影响因子：
11.1
作者：
BORRIELLO, F;KRAUTER, KS
通讯作者：
KRAUTER, KS