Human enteric defensins

Gene structure and developmental expression

Eric B. Mallow, Ann Harris, Nita Salzman, John P. Russell, Ralph J. DeBerardinis, Eduardo Ruchelli, Charles L Bevins

Research output: Contribution to journalArticle

233 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4038-4045
Number of pages8
JournalJournal of Biological Chemistry
Volume271
Issue number8
StatePublished - Feb 23 1996
Externally publishedYes

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Defensins
Developmental Genes
Paneth Cells
Genes
Small Intestine
Messenger RNA
Polymerase chain reaction
Pregnancy
Colon
Cell Count
RNA
RNA Isoforms
Polymerase Chain Reaction
Gene encoding
5' Flanking Region
RNA-Directed DNA Polymerase
Reverse Transcriptase Polymerase Chain Reaction
Microorganisms
In Situ Hybridization
Protein Isoforms

ASJC Scopus subject areas

  • Biochemistry

Cite this

Mallow, E. B., Harris, A., Salzman, N., Russell, J. P., DeBerardinis, R. J., Ruchelli, E., & Bevins, C. L. (1996). Human enteric defensins: Gene structure and developmental expression. Journal of Biological Chemistry, 271(8), 4038-4045.

Human enteric defensins : Gene structure and developmental expression. / Mallow, Eric B.; Harris, Ann; Salzman, Nita; Russell, John P.; DeBerardinis, Ralph J.; Ruchelli, Eduardo; Bevins, Charles L.

In: Journal of Biological Chemistry, Vol. 271, No. 8, 23.02.1996, p. 4038-4045.

Research output: Contribution to journalArticle

Mallow, EB, Harris, A, Salzman, N, Russell, JP, DeBerardinis, RJ, Ruchelli, E & Bevins, CL 1996, 'Human enteric defensins: Gene structure and developmental expression', Journal of Biological Chemistry, vol. 271, no. 8, pp. 4038-4045.
Mallow EB, Harris A, Salzman N, Russell JP, DeBerardinis RJ, Ruchelli E et al. Human enteric defensins: Gene structure and developmental expression. Journal of Biological Chemistry. 1996 Feb 23;271(8):4038-4045.
Mallow, Eric B. ; Harris, Ann ; Salzman, Nita ; Russell, John P. ; DeBerardinis, Ralph J. ; Ruchelli, Eduardo ; Bevins, Charles L. / Human enteric defensins : Gene structure and developmental expression. In: Journal of Biological Chemistry. 1996 ; Vol. 271, No. 8. pp. 4038-4045.
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