p15s (15-kD antimicrobial proteins) are stored in the secondary granules of Rabbit granulocytes: implications for antibacterial synergy with the bactericidal/permeability-increasing protein in inflammatory fluids.
p15s (15-kD antimicrobial proteins) are stored in the secondary granules of Rabbit granulocytes: implications for antibacterial synergy with the bactericidal/permeability-increasing protein in inflammatory fluids.
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DOI：
10.1182/blood.v89.2.672
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发表时间：
1997-01
期刊：
影响因子：
20.3
通讯作者：
K. Zarember;P. Elsbach;K. Shin-Kim;J. Weiss
中科院分区：
文献类型：
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作者：
K. Zarember;P. Elsbach;K. Shin-Kim;J. Weiss
兔糖原诱导的炎症性腹膜渗出液中多形核白细胞 (PMN) 释放的杀菌/通透性增加蛋白 (BPI) 对补体抗性大肠杆菌的杀菌效力取决于与细胞外 p15 的协同作用。这种协同作用取决于细胞外液中 p15s 与 BPI 的高摩尔比（约 50:1），大大超过细胞内的比率（约 5:1）。为了探索 p15 在炎症液体中大量积累的可能基础，我们检查了 BPI 和 p15 在 PMN 中的亚细胞定位。免疫金电子显微镜证实了BPI储存在初级颗粒中，并显示p15储存在次级颗粒中。密度分级兔骨髓细胞的逆转录聚合酶链反应证实，在骨髓分化过程中，p15s 的表达晚于 BPI。随着炎症反应的发展，p15 mRNA 比 BPI mRNA 更早出现在血液和渗出细胞中，这与骨髓中逐渐释放不太成熟的前体细胞一致。最后，Ca(2+)-离子载体介导的 p15 胞吐作用比 BPI 的释放更容易发生。因此，我们建议将 BPI (p15s) 的协同伙伴定位在更容易释放的次级颗粒中，使中性粒细胞能够在细胞外动员有效的 BPI 依赖性抗菌活性，而不会显着耗尽细胞内的 BPI 储备。
The bactericidal potency toward complement-resistant Escherichia coli of bactericidal/permeability-increasing protein (BPI) released from polymorphonuclear leukocytes (PMNs) in glycogen-induced inflammatory peritoneal exudates of rabbits is dependent on synergy with extracellular p15s. This synergy depends on the high molar ratio of p15s to BPI in the extracellular fluid (approximately 50:1), which greatly exceeds the intracellular ratio (approximately 5:1). To explore the possible basis of the greater accumulation of p15s in inflammatory fluid, we examined the subcellular localization of BPI and p15 in PMNs. Immunogold electron microscopy confirmed the storage of BPI in primary granules and showed that p15s are stored in secondary granules. Reverse-transcription polymerase chain reaction of density-fractionated rabbit bone marrow cells verified that p15s are expressed later than BPI during myeloid differentiation. As the inflammatory response evolves, p15 mRNA appears earlier in blood and exudate cells than mRNA for BPI, consistent with release of progressively less mature precursors from bone marrow. Finally, Ca(2+)-ionophore-mediated exocytosis of p15s occurs more readily than release of BPI. We therefore propose that localization of a synergistic partner of BPI (p15s) in more readily released secondary granules allows the neutrophil to mobilize potent BPI-dependent antibacterial activity extracellularly without significant depletion of intracellular BPI stores.