Enteric Infectious Disease in Neonates

Kinney, Janet S.; Eiden, Joseph

doi:10.1016/s0095-5108(18)30348-8

Cited by 9 publications

(3 citation statements)

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“…It has been suggested that immaturity of local intestinal defenses may contribute to the increased susceptibility of neonates to infections from luminal flora and to necrotizing enterocolitis (28,29). Therefore, we sought to more clearly characterize defensin expression in Paneth cells of the human small intestine, with a focus on fetal expression.…”

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confidence: 99%

Human Enteric Defensins

Mallow

Harris

Salzman

et al. 1996

Journal of Biological Chemistry

262

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Paneth cells, secretory epithelial cells of the small intestinal crypts, are proposed to contribute to local host defense. Both mouse and human Paneth cells express a collection of antimicrobial proteins, including members of a family of antimicrobial peptides named defensins. In this study, data from an anchored polymerase chain reaction (PCR) strategy suggest that only two defensin mRNA isoforms are expressed in the human small intestine, far fewer than the number expressed in the mouse. The two isoforms detected by this PCR approach were human defensin family members, HD-5 and HD-6. The gene encoding HD-6 was cloned and characterized. HD-6 has a genomic organization similar to HD-5, and the two genes have a striking pattern of sequence similarity localized chiefly in their proximal 5'-flanking regions. Analysis of human fetal RNA by reverse transcriptase-PCR detected enteric defensin HD-5 mRNA at 13.5 weeks of gestation in the small intestine and the colon, but by 17 weeks HD-5 was restricted to the small intestine. HD-6 mRNA was detectable at 13.5-17 weeks of gestation in the small intestine but not in the colon. This pattern of expression coincides with the previously described appearance of Paneth cells as determined by ultrastructural approaches. Northern analysis of total RNA from small intestine revealed quantifiable enteric defensin mRNA in five samples from 19 24 weeks of gestation at levels approximately 40-250-fold less than those observed in the adult, with HD-5 mRNA levels greater than those of HD-6 in all samples. In situ hybridization analysis localized expression of enteric defensin mRNA to Paneth cells at 24 weeks of gestation, as is seen in the newborn term infant and the adult. Consistent with earlier morphological studies, the ratio of Paneth cell number per crypt was reduced in samples at 24 weeks of gestation compared with the adult, and this lower cell number partially accounts for the lower defensin mRNA levels as determined by Northern analysis. Low levels of enteric defensin expression in the fetus may be characteristic of an immaturity of local defense, which is thought to predispose infants born prematurely to infection from intestinal microorganisms.

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mentioning

confidence: 99%

Human Enteric Defensins

Mallow

Harris

Salzman

et al. 1996

Journal of Biological Chemistry

262

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“…When the tissue COX protein content was determined, the newborn small bowel tissue had a significantly reduced COX-1 content than the adult. Interestingly, gastric lesions during endotoxemia are rarely seen clinically, as compared with the small bowel (1,2).…”

Section: Figmentioning

confidence: 99%

“…It is widely recognized that newborns are more susceptible to localized and disseminated infection than adults (1). This greater vulnerability early in life is in part related to the rather immature immunologic system of the neonate.…”

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confidence: 99%

Age‐Dependent Changes in the Regulation of Cyclooxygenases in the Gastrointestinal Tract After Gram‐Negative Endotoxemia

Martinez,

Reno,

Trevenen

et al. 2001

J. pediatr. gastroenterol. nutr.

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BackgroundCyclooxygenases (COXs) modulate prostaglandin synthesis in the gastrointestinal tract. Prostaglandins have been shown to have a cytoprotective effect on bowel mucosa in adults, but no similar data are available in neonates. Thus, the purpose of the current study was to evaluate age‐dependent changes in gastrointestinal tract COX regulation after Escherichia coli lipopolysaccharide exposure in rats.MethodsStomach, small bowel, and large bowel COX‐1 and COX‐2 mRNA levels (reverse transcription polymerase chain reaction technique) and protein content (Western blot) were obtained from neonates (younger than 3 days old) and adult rats 18 hours after exposure to E. coli O111:B4 lipopolysaccharide toxin. Untreated animals served as controls.ResultsStomach, small bowel, and large bowel tissue COX‐1 mRNA levels in the newborn were significantly lower (P < 0.01) than in the adult. No age‐dependent differences were found for COX‐2 mRNA levels. After lipopolysaccharide exposure, no significant changes in COX‐1 levels were seen at either age, whereas COX‐2 mRNA levels were increased only in the stomach for both ages. Western blot analysis of small bowel tissue for COX‐1 and COX‐2 showed no lipopolysaccharide‐induced changes in protein content, but the COX‐1 content was significantly lower in the newborn (P < 0.01).ConclusionsIn the rat, COX expression in the gastrointestinal tract is regulated in an age‐dependent fashion. Lower COX‐1 expression and a lack of observable increase in COX‐2 mRNA levels in the newborn small bowel after endotoxemia may render the bowel more susceptible to bowel injury early in life.

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