Contribution of different placental cells to the expression and stimulation of antimicrobial proteins (AMPs)

Contribution of different placental cells to the expression and stimulation of antimicrobial proteins (AMPs)
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DOI:
10.1016/j.placenta.2011.08.004
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发表时间:
2011-11-01
期刊:
影响因子:
3.8
通讯作者:
Schnare, M.
Schnare, M.
中科院分区:
医学3区
文献类型:
--
作者:
Klaffenbach, D.;Friedrich, D.;Schnare, M.

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胎盘是防止潜在传染源在怀孕期间引起胎儿疾病或相关并发症的主要屏障。因此,我们假设胎盘可能表达广泛的抗菌蛋白以及炎症趋化因子和细胞因子来对抗入侵的微生物。在这里,我们证明胎盘细胞确实表达多种 AMP(抗菌肽和蛋白质),包括杀菌/通透性增加蛋白 (BPI)、分泌性白细胞蛋白酶抑制剂 (SLPI)、人 β-防御素 2 (hBD2)、酰氧基酰基水解酶 (AOAH) 和导管素 (CAP18)。此外,这些细胞在细菌配体刺激下还分泌促炎细胞因子和趋化因子。值得注意的是,我们发现胎盘细胞的 BPI 表达可以完全归因于粒细胞,而高度纯化的胎盘滋养层仅表达 AMP 的一个子集,如 SLPI。出乎意料的是,滋养层 AMP 并未表现出响应各种 TLR 配体的诱导分泌,进一步研究表明滋养层对脂多糖 (LPS) 无反应是由于 TLR4 表达缺乏。总之,我们已经证明不同的 AMP 表达可以分配给胎盘中的不同细胞,胎盘细胞表达的 AMP 库是白细胞以及胚胎来源细胞合作的结果。 (C) 2011 Elsevier Ltd. 保留所有权利。
The placenta is a major barrier that prevents potentially infectious agents from causing fetal diseases or related complications during pregnancy. Therefore, we postulated that the placenta might express a broad repertoire of antimicrobial proteins as well as inflammatory chemokines and cytokines to combat invading microorganisms. Here we demonstrate that placental cells indeed express a wide range of AMPs (antimicrobial peptides and proteins) including bactericidal/permeability-increasing protein (BPI), secretory leukocyte protease inhibitor (SLPI), human beta-defensin 2 (hBD2), acyloxyacyl hydrolase (AOAH), and cathelicidin (CAP18). In addition, these cells also secrete pro-inflammatory cytokines and chemokines upon stimulation with bacterial ligands. Notably, we show that BPI expression by placental cells could be completely attributed to granulocytes while highly purified placental trophoblasts expressed only a subset of the AMPs like SLPI. Unexpectedly, trophoblast AMPs did not exhibit inducible secretion in response to various TLR ligands and further investigations showed that the unresponsiveness of trophoblasts to lipopolysaccharide (LPS) was due to a lack of TLR4 expression. In summary, we have shown that the expression of different AMPs can be allocated to various cells in the placenta and the repertoire of the AMPs expressed by placental cells is a result of a cooperation of leukocytes as well as cells from embryonic origin. (C) 2011 Elsevier Ltd. All rights reserved.