Absence of lysozyme (muramidase) in the intestinal Paneth cells of newborn infants with necrotising enterocolitis

Coutinho, H.B.; Mota, H. Carmona da; Coutinho, V. B.; Robalinho, T. I.; Furtado, André Freire; Walker, E; King, George; Mahida, Yashwant R.; Sewell, Herb F.; Wakelin, D.

doi:10.1136/jcp.51.7.512

Cited by 93 publications

(67 citation statements)

References 13 publications

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“…Based on the concurrent increased risk for NEC in premature infants, an association of PC immaturity with NEC was proposed. In support of this concept, a decreased lysozyme content was found by immunostain in NEC patients [145]. We found that in NEC patients, increased PC numbers and expression of defensin HD5 mRNA were not paralleled by a similar increase in HD5 peptide [146].…”

Section: Intestinal Metaplasia and Inflammatory Bowel Disease Involvementioning

confidence: 62%

The multifaceted Paneth cell

Porter

Bevins

Ghosh

et al. 2002

Cellular and Molecular Life Sciences (CMLS)

358

275

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Paneth cells (PCs) were described over a century ago as granulated cells located at the base of small intestinal crypts, the 'crypts of Lieberkühn.' Various histochemical staining procedures were developed that identified PCs based on their distinctive granule-staining pattern. Early on, PCs were proposed to perform a specialized function other than absorption of digested nutrients, the predominant task of the small intestinal epithelium. Since then, many constituents of the PC granules have been biochemically characterized. The presence of various granule-associated antimicrobial substances and their release upon microbial challenge suggest that PCs function as specialized defense cells in the small intestine. Altered resistance to microbial infection in animal models with disrupted or augmented PC function provides further support for the host defense role of PCs. Other PC components suggest that PCs may also participate in the regulation of lumenal ionic composition, crypt development, digestion, and intestinal inflammation.

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Section: Intestinal Metaplasia and Inflammatory Bowel Disease Involvementioning

confidence: 62%

The multifaceted Paneth cell

Porter

Bevins

Ghosh

et al. 2002

Cellular and Molecular Life Sciences (CMLS)

358

275

View full text Add to dashboard Cite

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“…This model could therefore be used to understand the pathogenesis of acute inflammatory conditions occurring perinatally, such as necrotizing enterocolitis. Indeed, it has been shown that a defect in Paneth cells is correlated with necrotizing enterocolitis of newborn infants (33). Moreover, a weak expression of Paneth cells defensins has been reported in CD patients (34), with a more pronounced decrease in patients carrying a NOD2 mutation.…”

Section: Discussionmentioning

confidence: 99%

Maturation of Paneth Cells Induces the Refractory State of Newborn Mice toShigellaInfection

Fernandez

Regnault

Mulet

et al. 2008

The Journal of Immunology

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The intestinal tract of adult mice is naturally resistant to infection by Shigella, the causative agent of bacillary dysentery in humans. Conversely, newborn mice are highly susceptible to intragastric Shigella infection and develop inflammatory lesions of the jejunal mucosa, very similar to those observed in the colon of dysenteric patients. However, the susceptibility period is short and one week after birth, animals have acquired a status of resistance characteristic of adult animals. To identify the developmental changes controlling the switch from disease susceptibility to resistance, we performed global gene expression analysis on noninfected and infected intestinal tissues taken from 4-day- and 7-day-old animals. Transcriptomic analysis of 4-day-old mice infected with the invasive Shigella strain showed a profile reflecting a strong inflammatory response with no evidence for retro-control, suggesting that the invasive process had occurred, whereas inflammation had been controlled after infection with the noninvasive strain. Differences in gene expression profiles between noninfected 4-day- and 7-day-old mice corresponded mainly to genes encoding anti-microbial peptides and proteases, suggesting that these molecules could be candidates for host antimicrobial resistance in the course of shigellosis. Indeed, expression of genes specific of Paneth cells was higher in 7-day- than in 4-day-old mice, and histological analysis indicated that Paneth cells were present only at day 7. Finally, using Sox9flox/flox-vil-cre mice, we showed that depletion of Paneth cells restored the susceptibility to Shigella of 7-day-old mice, clearly indicating that Paneth cells development is crucial for the clearance of intestinal infection.

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“…In patients with inflammatory bowel disease, for example, high colonic levels of the proinflammatory cytokines IL-8, IL-6, IL-1␤, and TNF-␣ (29) induced increased neutrophil activity that correlates with disease severity (30). It also is possible that the developmentally normal deficiency of Paneth cells and their secretory products in the neonatal period of the human predisposes some premature infants to necrotizing enterocolitis, an inflammatory disease of the intestine related to deficiency in innate immunity (31)(32)(33). Here again, the complex interplay among cell types of the intestinal mucosa in the inflammatory response may critically involve the antimicrobial and proinflammatory activities of the pore-forming Paneth cell ␣-defensins.…”

Section: Discussionmentioning

confidence: 99%