Enteric defensin expression in necrotizing enterocolitis. Pediatr Res 1998 Jul;44(1):20-6
Date
07/17/1998Pubmed ID
9667365DOI
10.1203/00006450-199807000-00003Scopus ID
2-s2.0-0031844367 (requires institutional sign-in at Scopus site) 114 CitationsAbstract
Immaturity of local innate defenses has been suggested as a factor involved in the pathophysiology of necrotizing enterocolitis (NEC). The mRNA of enteric human defensins 5 (HD5) and 6 (HD6), antibiotic peptides expressed in Paneth cells of the small intestine, have significantly lower levels of expression in fetal life compared with the term newborn and adult. In the current study, intracellular HD5 was demonstrated by immunohistochemistry at 24 wk of gestation, but at low levels, consistent with findings at the mRNA level. These data suggest that the low level enteric defensin expression, characteristic of normal intestinal development, may contribute to the immaturity of local defense, which predisposes the premature infant to NEC. To test if levels of defensin expression are altered in NEC, specimens from six cases of patients with NEC and five control subjects (four patients with atresia and one with meconium ileus) were analyzed to determine HD5 and HD6 mRNA levels by in situ hybridization. Compared with the control group, the level of enteric defensin expression per Paneth cell assessed by image analysis was increased 3-fold in cases of NEC (p = 0.02, analysis of variance and covariance). In addition, the number of Paneth cells was increased 2-fold in the small intestinal crypts of NEC specimens compared with those of control subjects (p < 0.01, covariance analysis). In healthy tissue, peptide levels within Paneth cells paralleled mRNA levels through development. In tissue from infants with NEC, the steady state level of intracellular peptide was not increased in conjunction with the observed rise in defensin mRNA. A straightforward interpretation of this finding is that HD5 is actively secreted in this setting and the Paneth cells maintain a constant steady state level of intracellular peptide, but the possibility of translational regulation of peptide expression is also consistent with these data. The associations between NEC and enteric defensin expression reported here offer support for future studies to address the role of these endogenous host defense factors in the pathophysiology of this disease.
Author List
Salzman NH, Polin RA, Harris MC, Ruchelli E, Hebra A, Zirin-Butler S, Jawad A, Martin Porter E, Bevins CLAuthor
Nita H. Salzman MD, PhD Director, Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdultAnalysis of Variance
Blood Bactericidal Activity
Blood Proteins
Defensins
Enterocolitis, Pseudomembranous
Fetus
Gene Expression Regulation, Developmental
Gestational Age
Humans
In Situ Hybridization
Infant
Infant, Newborn
Intestine, Small
Paneth Cells
RNA, Messenger
Reference Values
Transcription, Genetic