Paneth cell ablation in the presence of Klebsiella pneumoniae induces necrotizing enterocolitis (NEC)-like injury in the small intestine of immature mice
SUMMARY 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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
The Company of Biologists
2012-07-01
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| Series: | Disease Models & Mechanisms |
| Online Access: | http://dmm.biologists.org/content/5/4/522 |
| _version_ | 1818422804533477376 |
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| author | Chunxian Zhang Michael P. Sherman Lawrence S. Prince David Bader Jörn-Hendrik Weitkamp James C. Slaughter Steven J. McElroy |
| author_facet | Chunxian Zhang Michael P. Sherman Lawrence S. Prince David Bader Jörn-Hendrik Weitkamp James C. Slaughter Steven J. McElroy |
| author_sort | Chunxian Zhang |
| collection | DOAJ |
| description | SUMMARY
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. |
| first_indexed | 2024-12-14T13:32:05Z |
| format | Article |
| id | doaj.art-3b4285baff0e4fb4967bb3478b3ae3a0 |
| institution | Directory Open Access Journal |
| issn | 1754-8403 1754-8411 |
| language | English |
| last_indexed | 2024-12-14T13:32:05Z |
| publishDate | 2012-07-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Disease Models & Mechanisms |
| spelling | doaj.art-3b4285baff0e4fb4967bb3478b3ae3a02022-12-21T22:59:40ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112012-07-015452253210.1242/dmm.009001009001Paneth cell ablation in the presence of Klebsiella pneumoniae induces necrotizing enterocolitis (NEC)-like injury in the small intestine of immature miceChunxian ZhangMichael P. ShermanLawrence S. PrinceDavid BaderJörn-Hendrik WeitkampJames C. SlaughterSteven J. McElroySUMMARY 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.http://dmm.biologists.org/content/5/4/522 |
| spellingShingle | Chunxian Zhang Michael P. Sherman Lawrence S. Prince David Bader Jörn-Hendrik Weitkamp James C. Slaughter Steven J. McElroy Paneth cell ablation in the presence of Klebsiella pneumoniae induces necrotizing enterocolitis (NEC)-like injury in the small intestine of immature mice Disease Models & Mechanisms |
| title | Paneth cell ablation in the presence of Klebsiella pneumoniae induces necrotizing enterocolitis (NEC)-like injury in the small intestine of immature mice |
| title_full | Paneth cell ablation in the presence of Klebsiella pneumoniae induces necrotizing enterocolitis (NEC)-like injury in the small intestine of immature mice |
| title_fullStr | Paneth cell ablation in the presence of Klebsiella pneumoniae induces necrotizing enterocolitis (NEC)-like injury in the small intestine of immature mice |
| title_full_unstemmed | Paneth cell ablation in the presence of Klebsiella pneumoniae induces necrotizing enterocolitis (NEC)-like injury in the small intestine of immature mice |
| title_short | Paneth cell ablation in the presence of Klebsiella pneumoniae induces necrotizing enterocolitis (NEC)-like injury in the small intestine of immature mice |
| title_sort | paneth cell ablation in the presence of klebsiella pneumoniae induces necrotizing enterocolitis nec like injury in the small intestine of immature mice |
| url | http://dmm.biologists.org/content/5/4/522 |
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