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Bombesin Prevents the Atrophy of Peyer's Patches and the Dysfunction of M Cells in Rabbits Receiving Long-Term Parenteral Nutrition

Yoshinori Fujimura, MD^*, Ken Haruma, MD and Robert L. Owen, MD

From the ^* Department of Internal Medicine, Center for Gastroenterology and Endoscopy, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan; Division of Gastroenterology, Department of Medicine, Kawasaki Medical School, Kurashiki City, Okayama, Japan; and the Gastroenterology Section, Department of Medicine, VAMC and University of California, San Francisco, California

Correspondence: Yoshinori Fujimura, MD, Department of Internal Medicine, Center for Gastroenterology and Endoscopy, Kawasaki Hospital, Kawasaki Medical School, 2–1-80 Nakasange, Okayama City, Okayama 700-8505 Japan. Electronic mail may be sent to fujimura{at}kawasaki-hp.jp.

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 µg/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 10¹⁰/mL of 0.5-µm 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.

Journal of Parenteral and Enteral Nutrition, Vol. 31, No. 2, 75-85 (2007)
DOI: 10.1177/014860710703100275


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