Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 14, 2017; 23(42): 7531-7540
Published online Nov 14, 2017. doi: 10.3748/wjg.v23.i42.7531
Induction of precocious intestinal maturation in T-cell deficient athymic neonatal rats
Ester Arévalo Sureda, Catherine Gidlund, Björn Weström, Olena Prykhodko
Ester Arévalo Sureda, Catherine Gidlund, Björn Weström, Olena Prykhodko, Department of Biology, Faculty of Science, Lund University, Lund 22362, Sweden
Author contributions: Weström B and Prykhodko O conceived and designed the work; Arévalo Sureda E and Prykhodko O collected the data; Arévalo Sureda E and Gidlund C analysed the data; Arévalo Sureda E, Gidlund C, Weström B and Prykhodko O interpreted the data; Arévalo Sureda E drafted the manuscript; Weström B and Prykhodko O critically reviewed the article; Arévalo Sureda E, Gidlund C, Weström B and Prykhodko O approved the final version of the manuscript.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of Malmö-Lund Ethical Review Committee for Animal Experimentation, conducted in accordance with the European Community regulation concerning the protection of experimental animals (2010/63/EU) and protocol number M169-14.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Supported by the Royal Physiographic Society in Lund, Sweden to Arévalo Sureda E and Director Albert Påhlssons Foundation in Malmö Sweden to Prykhodko O.
Correspondence to: Ester Arévalo Sureda, PhD, Department of Biology, Lund University, Sölvegatan 35C, Lund 22362 Sweden. ester.arevalo_sureda@biol.lu.se
Telephone: +46-46-2229354
Received: May 23, 2017
Peer-review started: May 24, 2017
First decision: July 17, 2017
Revised: July 31, 2017
Accepted: September 13, 2017
Article in press: September 13, 2017
Published online: November 14, 2017
Processing time: 172 Days and 15.8 Hours
Abstract
AIM

To investigate whether gut maturation could be induced precociously in an athymic T-cell deficient neonatal rat model.

METHODS

Fourteen day-old athymic (nude) rats (NIH-Foxn1rnu) were gavaged with either phytohaemagglutinin - a lectin from red kidney beans (PHA); trypsin - a protease (Prot); or water - vehicle (control) as a single dose on one day or once a day for 3-day. The nude rats were either nurtured by their mothers or cross-fostered by conventional foster dams of the Sprague-Dawley strain from days 3-5 after birth. At 17 d of age, 72 h after administration of the first treatment, intestinal macromolecular permeability was tested in vivo, prior to euthanasia, after which blood and gut organs were sampled.

RESULTS

Provocation with both, PHA and protease, resulted in increased gut growth and maturation in nude rat pups independent of nursing. Foetal-type enterocytes were replaced by non-vacuolated adult-type enterocytes in the distal small intestine epithelium. Decreased intestinal macromolecular permeability (gut closure) was observed, with reduced permeability markers (BIgG and BSA, P < 0.001) in circulation. Increased pancreatic function, with an increased trypsin to protein ratio in pancreas homogenates, was observed independent of nursing in the nude pups. Immunostaining showed the presence of a few CD3+-cells in the intestinal mucosa of the nude pups. The number of CD3+-cells remained unaltered by provocation and no differences were observed between the nursing sets. Growth and vitality of the nude pups were dependent on nurturing, since cross-fostering by conventional dams increased their macromolecular absorptive capacity (BSA, P < 0.05), as well as their passive immunity (RIgG, P < 0.05).

CONCLUSION

Precocious gut maturation can be induced by enteral provocation in athymic rat pups, similarly to in euthymic pups, thus showing an independence from thymus-derived T-cells.

Keywords: Gut; Intestinal permeability; Passive immunity; Pancreas; Immunoglobulin G

Core tip: The rat is born with an immature gut and is thus a suitable model to study gut development. Enteral provocation with phytohaemagglutinin or protease induces precocious gut maturation in conventional (euthymic) rats. It has been suggested that T-lymphocytes are required for gut digestive maturation. The current study showed that precocious gut maturation could be induced by enteral provocation in athymic nude rats similar to that which occurs in euthymic rats. The few intestinal mucosal CD3+-T-cells that were observed in the athymic nude rats appeared to be unaffected by enteral provocation. The intestinal absorptive capacity in nude pups was enhanced when nurtured by conventional (immunocompetent) foster dams.