Journal article
Paneth cells and necrotizing enterocolitis: a novel hypothesis for disease pathogenesis
Neonatology (Basel, Switzerland), Vol.103(1), pp.10-20
2013
DOI: 10.1159/000342340
PMCID: PMC3609425
PMID: 23006982
Abstract
Current models of necrotizing enterocolitis (NEC) propose that intraluminal microbes destroy intestinal mucosa and activate an inflammatory cascade that ends in necrosis. We suggest an alternate hypothesis wherein NEC is caused by injury to Paneth cells (PCs) in the intestinal crypts. PCs are specialized epithelia that protect intestinal stem cells from pathogens, stimulate stem cell differentiation, shape the intestinal microbiota, and assist in repairing the gut. Our novel model of NEC uses neonatal mice and ablates PCs followed by enteral infection. We contrast this model with other animal examples of NEC and the clinical disease. Selective destruction of PCs using dithizone likely releases tumor necrosis factor-α and other inflammatory mediators. We propose that this event produces inflammation in the submucosa, generates platelet-activating factor, and induces a coagulopathy. The role of PCs in NEC is consistent with the onset of disease in preterm infants after a period of PC-related maturation, the central role of PCs in crypt-related homeostasis, the anatomic location of pneumatosis intestinalis close to the crypts, and the proximity of PCs to occluded blood vessels that cause coagulation necrosis of the intestinal villi. We offer this hypothesis to promote new thoughts about how NEC occurs and its potential prevention.
Details
- Title: Subtitle
- Paneth cells and necrotizing enterocolitis: a novel hypothesis for disease pathogenesis
- Creators
- Steven J McElroy - Division of Neonatology, Department of Pediatrics, University of Iowa, Iowa City, Iowa, USAMark A UnderwoodMichael P Sherman
- Resource Type
- Journal article
- Publication Details
- Neonatology (Basel, Switzerland), Vol.103(1), pp.10-20
- DOI
- 10.1159/000342340
- PMID
- 23006982
- PMCID
- PMC3609425
- ISSN
- 1661-7800
- eISSN
- 1661-7819
- Grant note
- R01 HD059127 / NICHD NIH HHS R44 HD057744 / NICHD NIH HHS K08 DK083677 / NIDDK NIH HHS
- Language
- English
- Date published
- 2013
- Academic Unit
- Microbiology and Immunology; Stead Family Department of Pediatrics
- Record Identifier
- 9984093315702771
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