Takeuchi K H, McGarry M P, Swank R T
Roswell Park Memorial Institute, Department of Molecular and Cellular Biology, Buffalo, New York 14263.
J Exp Med. 1987 Nov 1;166(5):1362-76. doi: 10.1084/jem.166.5.1362.
Elicited peritoneal neutrophils of beige (Chediak-Higashi) mice essentially lack activities of the neutral serine proteinases elastase and cathepsin G, which may explain the increased susceptibility to infection of beige mice and Chediak-Higashi patients. We have examined neutrophils of beige mice at earlier points in their development to determine if the proteinase genes are never expressed or whether they are expressed and then lost during neutrophil maturation. Surprisingly, bone marrow of beige mice had significant elastase and cathepsin G activity (approximately 60% of normal). The results of several experiments indicate that neutrophils were the sole source of elastase and cathepsin G in bone marrow. Neutral proteinase activity was readily demonstrable by histochemical procedures in beige marrow neutrophil precursors up to and including the metamyelocyte stage. However, mature neutrophils of beige marrow had greatly decreased activity. Also mature neutrophils (PMNs) of the peripheral circulation, like peritoneal neutrophils, had very low elastase and cathepsin C activities. Thus we conclude that beige neutrophil precursors express neutral proteinase activity, which is largely and irreversibly depleted by the time they fully mature in marrow.
米色（切迪阿克-希加什）小鼠的诱发性腹腔中性粒细胞基本上缺乏中性丝氨酸蛋白酶弹性蛋白酶和组织蛋白酶G的活性，这可能解释了米色小鼠和切迪阿克-希加什患者对感染易感性增加的原因。我们在米色小鼠发育的早期阶段检查了它们的中性粒细胞，以确定蛋白酶基因是从未表达，还是在中性粒细胞成熟过程中表达后又丢失。令人惊讶的是，米色小鼠的骨髓具有显著的弹性蛋白酶和组织蛋白酶G活性（约为正常水平的60%）。多项实验结果表明，中性粒细胞是骨髓中弹性蛋白酶和组织蛋白酶G的唯一来源。通过组织化学方法很容易在米色骨髓中性粒细胞前体直至包括晚幼粒细胞阶段检测到中性蛋白酶活性。然而，米色骨髓中的成熟中性粒细胞活性大大降低。外周循环中的成熟中性粒细胞（多形核白细胞），与腹腔中性粒细胞一样，弹性蛋白酶和组织蛋白酶C活性也非常低。因此我们得出结论，米色中性粒细胞前体表达中性蛋白酶活性，但在它们在骨髓中完全成熟时，这种活性在很大程度上且不可逆地耗尽。
