Paneth cell ablation in the presence of Klebsiella pneumoniae induces necrotizing enterocolitis (NEC)-like injury in the small intestine of immature mice.
Paneth cell ablation in the presence of Klebsiella pneumoniae induces necrotizing enterocolitis (NEC)-like injury in the small intestine of immature mice.
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DOI：
10.1242/dmm.009001
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发表时间：
2012-07
影响因子：
4.3
通讯作者：
McElroy SJ
中科院分区：
文献类型：
--
作者：
Zhang C;Sherman MP;Prince LS;Bader D;Weitkamp JH;Slaughter JC;McElroy SJ
坏死性小肠结肠炎（NEC）是早产儿发病和死亡的主要原因。在NEC发病过程中，细菌能够穿透先天免疫防御并侵入肠上皮层，导致随后的炎症和组织坏死。正常情况下，潘氏细胞出现在人类怀孕的前三个月的肠隐窝中。潘氏细胞通过产生多种抗微生物肽和促炎介质而构成先天免疫系统的主要组成部分。为了更好地理解Paneth细胞破坏在NEC中的可能作用，我们量化了NEC婴儿中存在的Paneth细胞数量，发现与年龄匹配的对照组相比，它们显著减少。我们能够通过用锌螯合剂双硫腙处理出生后第14- 16天（未成熟）小鼠的肠道来模拟这种损失。与对照组相比，双硫腙处理动物的肠道保留了大约一半的潘氏细胞数量。此外，通过将双硫腙治疗与暴露于肺炎克雷伯氏菌相结合，我们能够诱导类似于人类NEC的肠损伤和炎症诱导。此外，这种新的潘氏细胞消融模型产生NEC样病理，这与目前使用的其他动物模型一致，但这种技术使用更简单，可用于已被母鼠喂养的老年动物，并代表了一种新的研究NEC发病机制和治疗的研究路线。
Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality in premature infants. During NEC pathogenesis, bacteria are able to penetrate innate immune defenses and invade the intestinal epithelial layer, causing subsequent inflammation and tissue necrosis. Normally, Paneth cells appear in the intestinal crypts during the first trimester of human pregnancy. Paneth cells constitute a major component of the innate immune system by producing multiple antimicrobial peptides and proinflammatory mediators. To better understand the possible role of Paneth cell disruption in NEC, we quantified the number of Paneth cells present in infants with NEC and found that they were significantly decreased compared with age-matched controls. We were able to model this loss in the intestine of postnatal day (P)14-P16 (immature) mice by treating them with the zinc chelator dithizone. Intestines from dithizone-treated animals retained approximately half the number of Paneth cells compared with controls. Furthermore, by combining dithizone treatment with exposure to Klebsiella pneumoniae, we were able to induce intestinal injury and inflammatory induction that resembles human NEC. Additionally, this novel Paneth cell ablation model produces NEC-like pathology that is consistent with other currently used animal models, but this technique is simpler to use, can be used in older animals that have been dam fed, and represents a novel line of investigation to study NEC pathogenesis and treatment.
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影响因子：
2.4
作者：
Ford, H;Watkins, S;Rowe, M
通讯作者：
Rowe, M
影响因子：
4.2
作者：
Hambidge, K. Michael;Krebs, Nancy F.
通讯作者：
Krebs, Nancy F.
影响因子：
2.4
作者：
HIRAYAMA, K;MIYAJI, K;MITSUOKA, T
通讯作者：
MITSUOKA, T
影响因子：
8
作者：
Baker, SJ;Reddy, EP
通讯作者：
Reddy, EP
影响因子：
4.4
作者：
Leaphart, Cynthia L.;Cavallo, Jaime;Hackam, David J.
通讯作者：
Hackam, David J.