Novel anti-bacterial activities of β-defensin 1 in human platelets: suppression of pathogen growth and signaling of neutrophil extracellular trap formation.
Novel anti-bacterial activities of β-defensin 1 in human platelets: suppression of pathogen growth and signaling of neutrophil extracellular trap formation.
复制标题
DOI：
10.1371/journal.ppat.1002355
复制
发表时间：
2011-11
期刊：
影响因子：
6.7
通讯作者：
Weyrich AS
中科院分区：
文献类型：
--
作者：
Kraemer BF;Campbell RA;Schwertz H;Cody MJ;Franks Z;Tolley ND;Kahr WH;Lindemann S;Seizer P;Yost CC;Zimmerman GA;Weyrich AS
人β-防御素（hBD）是一种抑制微生物活性的抗菌肽。虽然hBD主要由上皮细胞表达，但我们发现人血小板表达具有预测和新颖抗菌活性的hBD-1。我们观察到活化的血小板围绕金黄色葡萄球菌（S。金黄色葡萄球菌），迫使病原体成簇，与S.单独的金黄色葡萄球菌。鉴于β-防御素的杀微生物活性，我们确定hBD家族成员是否存在于血小板中，并发现hBD-1的mRNA和蛋白质。我们还确定hBD-1蛋白存在于血小板的颗粒外细胞质区室中。与这种定位模式一致，引起血小板颗粒分泌的激动剂不容易诱导hBD-1释放。血小板在α毒素刺激下释放hBD-1。金黄色葡萄球菌的产物，使靶细胞透化。血小板衍生的hBD-1显著损害临床株S.金黄色。hBD-1还通过靶向多形核白细胞（PMN）诱导稳健的中性粒细胞胞外陷阱（NET）形成，这是先前未鉴定的β-防御素的新的抗微生物功能。综上所述，这些数据表明，hBD-1是一种以前未被认识到的血小板成分，显示出经典的抗微生物活性，此外，信号PMNs挤出DNA晶格，捕获和杀死细菌。血小板是血流中的小细胞，其主要功能是止血。除了凝血功能外，我们还发现人类血小板可以阻止细菌生长。血小板的这种抑制特性是由于β-防御素1，一种杀死细菌的小抗菌蛋白。β-防御素1还诱导白色血细胞释放蜘蛛网，捕获并杀死细菌。总之，这些发现表明人类血小板使用β-防御素1来抵抗细菌感染。
Human β-defensins (hBD) are antimicrobial peptides that curb microbial activity. Although hBD's are primarily expressed by epithelial cells, we show that human platelets express hBD-1 that has both predicted and novel antibacterial activities. We observed that activated platelets surround Staphylococcus aureus (S. aureus), forcing the pathogens into clusters that have a reduced growth rate compared to S. aureus alone. Given the microbicidal activity of β-defensins, we determined whether hBD family members were present in platelets and found mRNA and protein for hBD-1. We also established that hBD-1 protein resided in extragranular cytoplasmic compartments of platelets. Consistent with this localization pattern, agonists that elicit granular secretion by platelets did not readily induce hBD-1 release. Nevertheless, platelets released hBD-1 when they were stimulated by α-toxin, a S. aureus product that permeabilizes target cells. Platelet-derived hBD-1 significantly impaired the growth of clinical strains of S. aureus. hBD-1 also induced robust neutrophil extracellular trap (NET) formation by target polymorphonuclear leukocytes (PMNs), which is a novel antimicrobial function of β-defensins that was not previously identified. Taken together, these data demonstrate that hBD-1 is a previously-unrecognized component of platelets that displays classic antimicrobial activity and, in addition, signals PMNs to extrude DNA lattices that capture and kill bacteria. Platelets are small cells in the bloodstream whose primary function is to stop bleeding. In addition to their clotting functions, we show that human platelets stall bacterial growth. This inhibitory property of platelets is due to β-defensin 1, a small antimicrobial protein that kills bacteria. β-defensin 1 also induces white blood cells to discharge spider-like webs that trap and kill bacteria. Together, these findings indicate that human platelets use β-defensin 1 to fight off bacterial infection.
登录
查看更多内容
影响因子：
6.5
作者：
Peters, MJ;Dixon, G;Klein, NJ
通讯作者：
Klein, NJ
影响因子：
3.6
作者：
Fitzgerald, JR;Loughman, A;Foster, TJ
通讯作者：
Foster, TJ
影响因子：
0.7
作者：
ASHMARIN, IP;TKACHENKO, SB;KUBATIEV, AA
通讯作者：
KUBATIEV, AA
影响因子：
15.9
作者：
GANZ, T;SELSTED, ME;LEHRER, RI
通讯作者：
LEHRER, RI
DOI：
10.1161/atvbaha.107.152058
发表时间：
2008-02-01
影响因子：
8.7
作者：
Kerrigan, Steven W.;Clarke, Niamh;Cox, Dermot
通讯作者：
Cox, Dermot