Normal neutrophil function in cathepsin G-deficient mice
Normal neutrophil function in cathepsin G-deficient mice
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DOI：
10.1182/blood.v94.12.4282.424k45_4282_4293
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发表时间：
1999-12-15
期刊：
影响因子：
20.3
通讯作者：
Ley, TJ
中科院分区：
文献类型：
--
作者：
MacIvor, DM;Shapiro, SD;Ley, TJ
组织蛋白酶G是一种中性丝氨酸蛋白酶，在髓系发育的早幼粒细胞阶段高表达。我们开发了一种同源重组策略来创造小鼠组织蛋白酶G的功能缺失突变，由于该突变纯合小鼠的骨髓中没有检测到组织蛋白酶G蛋白或活性，表明骨髓细胞中没有其他蛋白具有相同的特异性。组织蛋白酶G-/-小鼠的造血功能正常，且无明显的凝血异常。来自组织蛋白酶G-/-小鼠的中性粒细胞具有正常的形态和天青颗粒组成；这些中性粒细胞也表现出正常的吞噬和超氧化物产生，并对C5a、fMLP和IL-8具有正常的趋化反应。尽管组织蛋白酶G此前已被证明具有广谱的抗生素特性，但对金黄色葡萄球菌、肺炎克雷伯菌或大肠杆菌感染的小鼠的挑战产生的存活结果与野生动物没有什么不同。综上所述，组织蛋白酶G-/-中性粒细胞在功能上没有明显的缺陷；这些正常的中性粒细胞功能都不需要组织蛋白酶G，或者具有不同特异性的相关天青颗粒蛋白(如中性粒细胞弹性蛋白酶、蛋白酶3、天青素等)可以在体内替代它。(C)1999年由美国血液病学会主办。
Cathepsin G is a neutral serine protease that is highly expressed at the promyelocyte stage of myeloid development. We have developed a homologous recombination strategy to create a loss-of-function mutation for murine cathepsin G, Bone marrow derived from mice homozygous for this mutation had no detectable cathepsin G protein or activity, indicating that no other protease in bone marrow cells has the same specificity. Hematopoiesis in cathepsin G-/- mice is normal, and the mice have no overt abnormalities in blood clotting. Neutrophils derived from cathepsin G-/- mice have normal morphology and azurophil granule composition; these neutrophils also display normal phagocytosis and superoxide production and have normal chemotactic responses to C5a, fMLP, and interleukin-8. Although cathepsin G has previously shown to have broad spectrum antibiotic properties, challenges of mice with Staphylococcus aureus, Klebsiella pneumoniae, or Escherichia coli yielded survivals that were not different from those of wild-type animals. In sum, cathepsin G-/- neutrophils have no obvious defects in function; either cathepsin G is not required for any of these normal neutrophil functions or related azurophil granule proteases with different specificities (ie, neutrophil elastase, proteinase 3, azurocidin, and/or others) can substitute for it in vivo. (C) 1999 by The American Society of Hematology.