Enterochromaffin cell hyperplasia and decreased serotonin transporter in a mouse model of postinfectious bowel dysfunction.
Patients with postinfective irritable bowel syndrome and Trichinella spiralis-infected mice share many features including visceral hypersensitivity and disordered motility. We assessed enterochromaffin (EC) numbers and serotonin transporter (SERT) using National Institute of Health (NIH) female mice studied for up to 56 days post-T. spiralis infection. The effects of steroid treatment and the T-cell dependence of the observed responses were assessed by infection of hydrocortisone-treated or T-cell receptor knock out [TCR (betaxdelta) KO] animals. Enterochromaffin cell density in uninfected animals increased from duodenum 10.0 cells mm-2 (5.9-41.0) to colon 61.8. (46.3-162) cells mm-2 P<0.0001. Infection increased duodenal and jejunal counts which rose to 37.3 (22-57.7) cells mm-2 and 50.6 (7-110.8) cells mm-2, respectively, at day 14. Infection significantly reduced jejunal SERT expression, with luminance values falling from 61.0 (45.1-98.3) to a nadir of 11.6 (0-36.0) units at day 9, P<0.001. Specific deficiencies in all T cells reduced EC hyperplasia and abrogated infection-induced mastocytosis. Thus infection induced inflammation increases EC numbers, as has been reported in PI-IBS, and reduces SERT. This may increase mucosal 5HT availability and contribute to the clinical presentation of PI-IBS.
Wheatcroft
J
J
Wolfson Digestive Diseases Centre, University Hospital, Nottingham, UK.
Wakelin
D
D
Smith
A
A
Mahoney
C R
CR
Mawe
G
G
Spiller
R
R
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D002452:Cell Count; D004064:Digestive System / Q000473:pathology* / Q000503:physiopathology*; D004759:Enterochromaffin Cells / Q000473:pathology*; D006854:Hydrocortisone / Q000627:therapeutic use; D006965:Hyperplasia / Q000473:pathology; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000473:pathology; D007583:Jejunum / Q000378:metabolism / Q000473:pathology; D008407:Mast Cells / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D014235:Trichinellosis / Q000473:pathology*
D000893:Anti-Inflammatory Agents; D050486:Serotonin Plasma Membrane Transport Proteins; D006854:Hydrocortisone