The human antibacterial cathelicidin, hCAP-18, is synthesized in myelocytes and metamyelocytes and localized to specific granules in neutrophils.
The human antibacterial cathelicidin, hCAP-18, is synthesized in myelocytes and metamyelocytes and localized to specific granules in neutrophils.
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DOI：
10.1182/blood.v90.7.2796.2796_2796_2803
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发表时间：
1997
期刊：
影响因子：
20.3
通讯作者：
O. Sørensen;K. Arnljots;J. Cowland;D. Bainton;N. Borregaard
中科院分区：
文献类型：
--
作者：
O. Sørensen;K. Arnljots;J. Cowland;D. Bainton;N. Borregaard
hCAP-18是被称为cathelicidins的抗菌和内毒素结合蛋白质家族的唯一人类成员。抗菌和内毒素结合结构域位于蛋白质（LL-37）的C-末端37个氨基酸，据信这是通过过氧化物酶阳性颗粒的蛋白酶从中和N-末端释放的。在人类中性粒细胞中，过氧化物酶阳性和过氧化物酶阴性颗粒可细分为蛋白质含量和被胞吐能力不同的颗粒亚群。为了确定hCAP-18的定位，我们在Percoll密度梯度上进行了高分辨率免疫电子显微镜和亚细胞分级。在分离的人骨髓细胞中研究hCAP-18的生物合成。发现hCAP-18在亚细胞级分中与乳铁蛋白共定位和共移动，但不与明胶酶共定位和共移动。这是通过电子显微镜证实的。hCAP-18在与乳铁蛋白相同的髓样细胞成熟阶段合成，并且有效地靶向颗粒。与过氧化物酶阴性颗粒的基质金属蛋白酶、胶原酶和明胶酶一样，hCAP-18也以未加工的形式储存。hCAP-18是特异性颗粒的主要蛋白质，其中它与乳铁蛋白以等摩尔比存在。
hCAP-18 is the only human member of the antibacterial and endotoxin-binding family of proteins known as cathelicidins. The antibacterial and endotoxin binding domains reside in the C-terminal 37 amino acids of the protein (LL-37) and this is believed to be unleashed from the neutralizing N-terminus by proteases from peroxidase positive granules. In human neutrophils, peroxidase positive and peroxidase negative granules can be subdivided into granule subsets that differ in protein content and ability to be exocytosed. To determine the localization of hCAP-18, we performed high-resolution immuno-electron microscopy and subcellular fractionation on Percoll density gradients. Biosynthesis of hCAP-18 was investigated in isolated human bone marrow cells. hCAP-18 was found to colocalize and comobilize with lactoferrin, but not with gelatinase in subcellular fractions. This was confirmed by electron microscopy. hCAP-18 is synthesized at the same stage of myeloid cell maturation as lactoferrin, and is efficiently targeted to granules. Like the peroxidase negative granule's matrix metalloproteinases, collagenase and gelatinase, hCAP-18 is also stored in unprocessed form. hCAP-18 is a major protein of specific granules where it is present in equimolar ratio with lactoferrin.