Chicken heterophils are recruited to the site of Salmonella infection and release antibacterial mature Cathelicidin-2 upon stimulation with LPS
Chicken heterophils are recruited to the site of Salmonella infection and release antibacterial mature Cathelicidin-2 upon stimulation with LPS
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DOI：
10.1016/j.molimm.2008.12.015
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发表时间：
2009-04-01
影响因子：
3.6
通讯作者：
Haagsman, Henk P.
中科院分区：
文献类型：
--
作者：
Van Dijk, Albert;Tersteeg-Zijderveld, Monique H. G.;Haagsman, Henk P.
禽类cathelicidins的生物学功能还不清楚。在哺乳动物中，cathelicidin已显示具有有效的广泛抗微生物活性以及免疫调节活性。因此，我们研究了Cathelicidin-2在未感染和沙门氏菌攻击的肉鸡中的杀微生物活性和定位。使用免疫组织化学，Cathelicidin-2被证明是丰富的异嗜性粒细胞，定位于大杆状颗粒，但在其他外周血细胞和肠上皮细胞缺席。观察到Cathelicidin-2的合成在早幼粒细胞阶段开始。感染后8 h内，在沙门氏菌感染的肉鸡空肠中观察到大量含Cathelicidin-2的嗜异性粒细胞浸润。异嗜性细胞显示在用Solmonello衍生的LPS刺激后以时间依赖性方式释放成熟的Cathelicidin-2肽。Cathelicidin-2前体的加工由具有二价阳离子依赖性的丝氨酸蛋白酶介导。Cathelicidin-2肽对所有测试的微生物（包括鸡特异性沙门氏菌分离株）显示出有效的杀菌和杀真菌活性。这些结果强调了禽类嗜异性粒细胞作为抵抗入侵病原体的第一道防线的重要性，并暗示通过嗜异性介导的释放，cathelicidins可能极大地促进禽类先天免疫。(C)2009爱思唯尔有限公司版权所有。
The biological functions of avian cathelicidins are poorly defined. In mammals, cathelicidins have shown to possess potent broad-range antimicrobial activity as well as immunomodulatory activities. Therefore, we investigated the microbicidal activities and localization of Cathelicidin-2 in non-infected and Salmonella-challenged broiler chickens. Using immunohistochemistry, Cathelicidin-2 was shown to be abundantly present in heterophils, localized in the large rod-shaped granules, but absent in other peripheral blood cells and intestinal epithelial cells. Cathelicidin-2 synthesis was observed to be initiated at the early promyelocyte stage. Considerable infiltration of Cathelicidin-2 containing heterophils was observed in the jejunum of Salmonella enteritidis-challenged broilers within 8 h post-infection. Heterophils were shown to release mature Cathelicidin-2 peptide upon stimulation with Solmonello-derived LPS in a time-dependent way. Processing of the Cathelicidin-2 precursor was mediated by serine proteases with a divalent cation dependency. Cathelicidin-2 peptide showed potent bactericidal and fungicidal activity against all tested microorganisms, including chicken-specific Salmonella isolates. These results underscore the importance of avian heterophils as a first line of defence against invading pathogens and implicate that via heterophilmediated release, cathelicidins may greatly contribute to avian innate immunity. (C) 2009 Elsevier Ltd. All rights reserved.