title: Radiation enteropathy and leucocyte-endothelial cell reactions in a refined small bowel model.
abstract: BACKGROUND
  Leucocyte recruitment and inflammation are key features of high dose radiation-induced tissue injury. The inflammatory response in the gut may be more pronounced following radiotherapy due to its high bacterial load in comparison to the response in other organs. We designed a model to enable us to study the effects of radiation on leucocyte-endothelium interactions and on intestinal microflora in the murine ileum. This model enables us to study specifically the local effects of radiation therapy.
  
  
  METHODS
  A midline laparotomy was performed in male C57/Bl6 mice and a five-centimetre segment of ileum is irradiated using the chamber. Leucocyte responses (rolling and adhesion) were then analysed in ileal venules 2 - 48 hours after high dose irradiation, made possible by an inverted approach using intravital fluorescence microscopy. Furthermore, intestinal microflora, myeloperoxidase (MPO) and cell histology were analysed.
  
  
  RESULTS
  The highest and most reproducible increase in leucocyte rolling was exhibited 2 hours after high dose irradiation whereas leucocyte adhesion was greatest after 16 hours. Radiation reduced the intestinal microflora count compared to sham animals with a significant decrease in the aerobic count after 2 hours of radiation. Further, the total aerobic counts, Enterobacteriaceae and Lactobacillus decreased significantly after 16 hours. In the radiation groups, the bacterial count showed a progressive increase from 2 to 24 hours after radiation.
  
  
  CONCLUSIONS
  This study presents a refinement of a previous method of examining mechanisms of radiation enteropathy, and a new approach at investigating radiation induced leucocyte responses in the ileal microcirculation. Radiation induced maximum leucocyte rolling at 2 hours and adhesion peaked at 16 hours. It also reduces the microflora count, which then starts to increase steadily afterwards. This model may be instrumental in developing strategies against pathological recruitment of leucocytes and changes in intestinal microflora in the small bowel after radiotherapy.
authors.affiliation: Department of Surgery, Malmö University Hospital, Lund University, Malmö, Sweden. louis.johnson@skane.se
authors.forename: Louis Banka
authors.initials: LB
authors.lastname: Johnson
authors.forename: Amjid Ali
authors.initials: AA
authors.lastname: Riaz
authors.forename: Diya
authors.initials: D
authors.lastname: Adawi
authors.forename: Lena
authors.initials: L
authors.lastname: Wittgren
authors.forename: Sven
authors.initials: S
authors.lastname: Bäck
authors.forename: Charlotte
authors.initials: C
authors.lastname: Thornberg
authors.forename: Nadia
authors.initials: N
authors.lastname: Osman
authors.forename: Virgil
authors.initials: V
authors.lastname: Gadaleanu
authors.forename: Henrik
authors.initials: H
authors.lastname: Thorlacius
authors.forename: Bengt
authors.initials: B
authors.lastname: Jeppsson
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000502:physiology / Q000528:radiation effects; D002465:Cell Movement / Q000502:physiology / Q000528:radiation effects; D004727:Endothelium / Q000382:microbiology / Q000502:physiology / Q000528:radiation effects*; D007079:Ileitis / Q000473:pathology / Q000503:physiopathology*; D007082:Ileum / Q000098:blood supply / Q000382:microbiology / Q000528:radiation effects*; D007958:Leukocyte Count; D007962:Leukocytes / Q000201:enzymology / Q000502:physiology / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation; D023421:Models, Animal; D009195:Peroxidase / Q000032:analysis; D011833:Radiation Injuries, Experimental / Q000473:pathology / Q000503:physiopathology*
chemical_list: D009195:Peroxidase