EXTRACELLULAR RELEASE OF ANTIMICROBIAL DEFENSINS BY HUMAN POLYMORPHONUCLEAR LEUKOCYTES
EXTRACELLULAR RELEASE OF ANTIMICROBIAL DEFENSINS BY HUMAN POLYMORPHONUCLEAR LEUKOCYTES
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DOI：
10.1128/iai.55.3.568-571.1987
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发表时间：
1987-03-01
影响因子：
3.1
通讯作者：
GANZ, T
中科院分区：
文献类型：
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作者：
GANZ, T
人多形核白细胞（PMN）含有三种抗菌和细胞毒肽，属于哺乳动物粒细胞肽家族，称为防御素。为了确定其潜在的可用性为细胞外杀微生物或细胞毒性事件，我们量化的细胞外释放的防御素刺激后的人中性粒细胞与佛波醇肉豆蔻酸乙酸酯和调理酵母聚糖。通过酶免疫测定法测定并通过聚丙烯酰胺凝胶电泳和光密度测定法证实，106个人PMN含有4至5 μ g防御素。在用高浓度的佛波醇肉豆蔻酸酯乙酸酯（1 μ g/ml）刺激后，在培养基中发现约8%的PMN防御素。防御素的释放与嗜天青颗粒标志物β-葡萄糖醛酸酶或弹性蛋白酶的释放相关性最好，与特定颗粒标志物乳铁蛋白或细胞质乳酸脱氢酶的释放相关性较差。吞噬调理酵母多糖导致细胞外释放的PMN防御素少于3%。与其他嗜天青颗粒蛋白的释放相比，防御素向培养基中的释放较少的因素可能包括嗜天青颗粒的异质性和防御素对细胞表面和调理颗粒的亲和力。在体内，防御素是最有可能达到有效的杀微生物或细胞毒性浓度的PMN-丰富的渗出液（脓），在密闭的环境中的吞噬溶酶体，或在细胞间隙之间的PMN和它们的目标。
Human polymorphonuclear leukocytes (PMN) contain three antimicrobial and cytotoxic peptides which belong to a family of mammalian granulocyte peptides named defensins. To determine their potential availability for extracellular microbicidal or cytotoxic events, we quantified the extracellular release of defensins after stimulation of human PMN with phorbol myristate acetate and opsonized zymosan. As determined by enzyme immunoassay and confirmed by polyacrylamide gel electrophoresis and densitometry, 106 human PMN contained 4 to 5 .mu.g of defensins. After stimulation with a high concentration of phorbol myristate acetate (1 .mu.g/ml), about 8% of PMN defensins were found in the media. Release of defensins correlated best with the release of azurophil granule marker beta-glucuronidase or elastase and poorly with the release of either the specific granule marker lactoferrin or cytoplasmic lactate dehydrogenase. Phagocytosis of opsonized zymosan resulted in the extracellular release of less than 3% of PMN defensins. The factors responsible for less release of defensins into media relative to the release of other azurophil granule proteins may include heterogeneity of azurophil granules and the affinity of defensins for cellular surfaces and opsonized particles. In vivo, defensins are most likely to reach effective microbicidal or cytotoxic concentrations in PMN-rich exudates (pus), in confined environments of the phagolysosomes, or in intercellular clefts between PMN and their targets.