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. 2004 Feb;135(2):303-9.
doi: 10.1111/j.1365-2249.2004.02374.x.

Paneth cell granule depletion in the human small intestine under infective and nutritional stress

P Kelly  1 , R Feakins, P Domizio, J Murphy, C Bevins, J Wilson, G McPhail, R Poulsom, W Dhaliwal
Affiliations

Paneth cell granule depletion in the human small intestine under infective and nutritional stress

P Kelly et al. Clin Exp Immunol. 2004 Feb.

Abstract

Paneth cells are important contributors to the intestinal antimicrobial barrier through synthesis and release of antimicrobial peptides and proteins. Animal studies indicate that Paneth cell numbers, location and granule morphology are altered by infection and zinc status. We examined human tissue to determine whether Paneth cell numbers, distribution or granule morphology are altered in infective, inflammatory and nutritional disorders. Archival sections from infective disorders (giardiasis, cryptosporidiosis, HIV, helminth infection) were compared with active inflammatory conditions (coeliac, Crohn's and graft-versus-host diseases) and histologically normal tissues. A subset of tissues was studied by electron microscopy and TUNEL staining for apoptosis. Human defensin-5 (HD5) peptide and mRNA was analysed by immunohistochemistry, in situ hybridization and quantitative reverse transcription polymerase chain reaction. Sections from a tropical population cohort study were then analysed to determine the relationship of granule depletion to infection, nutritional status and plasma zinc concentration. In HIV-related cryptosporidiosis, but not other disorders, Paneth cells were reduced in number and markedly depleted of granules. Paneth cell granule depletion was associated with reduced HD5 immunoreactivity, but this was not due to apoptosis and there was no reduction in mRNA transcripts. In the tropical population studied, depletion of granules was associated with reduced body mass index, reduced plasma zinc levels and HIV infection. Paneth cell granules in human small intestine may be depleted in response to infective and nutritional stress. We postulate that this is one mechanism through which zinc status influences host susceptibility to intestinal infection.

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Figures

Fig. 1
Fig. 1
Single crypt marked to show the definition of zones used for counting.
Fig. 2
Fig. 2
Representative gel of competitive RT-PCR analysis for two samples (a,b). Four lanes are shown, with RT-PCR products from reactions beginning with 100 pg, 10 pg, 1 pg and 100 pg standard RNA loaded in lanes 1, 2, 3 and 4, respectively. The upper band is the standard RNA 430 base pairs (bp) product and the lower band the 206 bp product of the target RNA. The calculated quantity of HD5 mRNA in (a) was 5·3 × 107 transcripts/µg total RNA, and in (b) was 3·0 × 105 transcripts/µg total RNA.
Fig. 3
Fig. 3
Paneth cells stained with haematoxylin and eosin. (a) Normal Paneth cell granules with plump eosinophilic granules; (b) Paneth cells which have an empty appearance due to granule depletion.
Fig. 4
Fig. 4
Sections stained with anti-HD5 antibody, from normal intestine (a) and abnormal intestine showing Paneth cell granule depletion (b). In situ hybridization for mRNA (c,d) performed on serial sections from the same biopsies as (a) and (b), respectively, separated by at most 20 µm. Although the biopsy from which panels (b) and (d) were both taken shows depletion of HD5 peptide, mRNA does not appear to be reduced.
Fig. 5
Fig. 5
Electron microscopic appearance of Paneth cells from a section showing granule depletion. Granules are reduced in size and number and show pleiomorphism both in size and osmophilia, although these appearances were not generally as severe as the changes described previously [7,8].
See this image and copyright information in PMC

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References

    1. Ganz T. Paneth cells − guardians of the gut cell hatchery. Nature Immunol. 2000;1:99–100. - PubMed
    1. Keshav S, McKnight AJ, Arora R, Gordon S. Cloning of intestinal phospholipase A2 from intestinal epithelial RNA by differential display PCR. Cell Prolif. 1997;30:369–83. - PMC - PubMed
    1. Bevins CL, Porter EM, Ganz T. Defensins and innate host defence of the gastrointestinal tract. Gut. 1999;45:911–5. - PMC - PubMed
    1. Ayabe T, Satchell DP, Wilson CL, et al. Secretion of microbicidal alpha-defensins by intestinal Paneth cells in response to bacteria. Nature Immunol. 2000;1:113–8. - PubMed
    1. Ghosh D, Porter EM, Shen B, et al. Paneth cell trypsin is the processing enzyme for human defensin-5. Nat Immunol. 2002;3:583–90. - PubMed

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