title: The spleen responds to intestinal manipulation but does not participate in the inflammatory response in a mouse model of postoperative ileus.
abstract: BACKGROUND
  Postoperative ileus is characterized by a transient impairment of the gastrointestinal motility after abdominal surgery. The intestinal inflammation, triggered by handling of the intestine, is the main factor responsible for the prolonged dysmotility of the gastrointestinal tract. Secondary lymphoid organs of the intestine were identified as essential components in the dissemination of inflammation to the entire gastrointestinal tract also called field effect. The involvement of the spleen, however, remains unclear.
  
  
  OBJECTIVE
  In this study, we investigated whether the spleen responds to manipulation of the intestine and participates in the intestinal inflammation underlying postoperative ileus.
  
  
  METHODS
  Mice underwent Laparotomy (L) or Laparotomy followed by Intestinal Manipulation (IM). Twenty-four hours later, intestinal and colonic inflammation was assessed by QPCR and measurement of the intestinal transit was performed. Analysis of homeostatic chemokines in the spleen was performed by QPCR and splenic cell populations analysed by Flow Cytometry. Blockade of the egress of cells from the spleen was performed by administration of the Sphingosine-1-phosphate receptor 1 (S1P1) agonist CYM-5442 10 h after L/IM.
  
  
  RESULTS
  A significant decrease in splenic weight and cellularity was observed in IM mice 24 h post-surgery, a phenomenon associated with a decreased splenic expression level of the homeostatic chemokine CCL19. Splenic denervation restored the expression of CCL19 and partially prevented the reduction of splenocytes in IM mice. Treatment with CYM-5442 prevented the egress of splenocytes but did not ameliorate the intestinal inflammation underlying postoperative ileus.
  
  
  CONCLUSIONS
  Intestinal manipulation results in two distinct phenomena: local intestinal inflammation and a decrease in splenic cellularity. The splenic response relies on an alteration of cell trafficking in the spleen and is partially regulated by the splenic nerve. The spleen however does not participate in the intestinal inflammation during POI.
authors.affiliation: Tytgat Institute for Liver and Intestinal Research, Academic medical center (AMC), Amsterdam, The Netherlands.
authors.forename: Léa M M
authors.initials: LM
authors.lastname: Costes
authors.affiliation: Tytgat Institute for Liver and Intestinal Research, Academic medical center (AMC), Amsterdam, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: van der Vliet
authors.affiliation: Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Belgium.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Farro
authors.affiliation: Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Belgium.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Matteoli
authors.affiliation: Tytgat Institute for Liver and Intestinal Research, Academic medical center (AMC), Amsterdam, The Netherlands.
authors.forename: Sjoerd H W
authors.initials: SH
authors.lastname: van Bree
authors.affiliation: Tytgat Institute for Liver and Intestinal Research, Academic medical center (AMC), Amsterdam, The Netherlands; Adaptive Immunity Lab, Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory AMC/UvA, Amsterdam, The Netherlands.
authors.forename: Brenda J
authors.initials: BJ
authors.lastname: Olivier
authors.affiliation: Adaptive Immunity Lab, Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory AMC/UvA, Amsterdam, The Netherlands.
authors.forename: Martijn A
authors.initials: MA
authors.lastname: Nolte
authors.affiliation: Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Belgium.
authors.forename: Guy E
authors.initials: GE
authors.lastname: Boeckxstaens
authors.affiliation: Tytgat Institute for Liver and Intestinal Research, Academic medical center (AMC), Amsterdam, The Netherlands.
authors.forename: Cathy
authors.initials: C
authors.lastname: Cailotto
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005769:Gastrointestinal Motility / Q000187:drug effects; D006801:Humans; D045823:Ileus / Q000503:physiopathology / Q000601:surgery*; D007189:Indans / Q000008:administration & dosage; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000503:physiopathology / Q000601:surgery*; D008297:Male; D051379:Mice; D010069:Oxadiazoles / Q000008:administration & dosage; D011183:Postoperative Complications / Q000378:metabolism / Q000473:pathology; D011184:Postoperative Period; D049349:Receptors, Lysosphingolipid / Q000037:antagonists & inhibitors; D013154:Spleen / Q000187:drug effects / Q000378:metabolism*
chemical_list: C532995:2-(4-(5-(3,4-diethoxyphenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl amino)ethanol; D007189:Indans; D010069:Oxadiazoles; D049349:Receptors, Lysosphingolipid