Bombesin prevents the atrophy of Peyer's patches and the dysfunction of M cells in rabbits receiving long-term parenteral nutrition

Abstract

Background: Long-term parenteral nutrition (PN) induces atrophy of the gut-associated lymphoid tissue (GALT). We examined whether bombesin could ameliorate this atrophy of Peyer's patches and the down-regulation of particle transport by M cells, which was also observed in rabbits undergoing PN.

Methods: Adult female rabbits were randomized into 6 groups to receive chow ad libitum, chow + bombesin, PN, or PN + bombesin (20 microg/kg, subcutaneously every 8 hours) for 2 or 4 weeks. At the end of each nutrition period, a laparotomy was performed under anesthesia and a suspension of 1 x 10(10)/mL of 0.5-microm fluorescent microspheres was injected into the lumen of intestinal segments containing Peyer's patches and incubated for 2 hours. After the incubation, segments were harvested and prepared for light microscopy, immunohistochemistry, fluorescent microscopy, and electron microscopy.

Results: Long-term PN reduced the size of ileal Peyer's patches, the number of microspheres that was taken up into the follicle-associated epithelium of lymphoid nodules, and the area of Peyer's patch surface occupied by M cells. The number of intraepithelial lymphocytes within the follicle-associated epithelium near the perifollicular crypts of Peyer's patches was also reduced by long-term PN. These consequences were dramatically ameliorated by treatment with bombesin. No ultrastructural alteration of the M cells of Peyer's patches was found in the chow, the PN, or the PN + bombesin groups.

Conclusions: Bombesin prevents PN-induced atrophy of GALT, reduction of M cell numbers, and decrease in particulate transport by M cells during long-term PN. Bombesin may modulate the genesis of and particulate transport by M cells through stimulation of lymphoid cells in Peyer's patch epithelium near perifollicular crypts, where M cells and other constituents of lymphoid follicle epithelium are generated, thereby preserving mucosal immunity.