Selective jejunal manipulation causes postoperative pan-enteric inflammation and dysmotility

Schwarz, Nicolas T.; Kalff, Jörg C.; Türler, Andreas; Speidel, Nicola; Grandis, Jennifer R.; Billiar, Timothy R.; Bauer, Anthony J.

doi:10.1053/j.gastro.2003.10.060

Cited by 158 publications

(131 citation statements)

References 27 publications

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“…11 A previous work of our group shows by the use of the present methods that immunocytes from intestinally manipulated small bowel disseminate to the unmanipulated colon.…”

Section: Discussionmentioning

confidence: 65%

Functional Assessment of Intestinal Motility and Gut Wall Inflammation in Rodents: Analyses in a Standardized Model of Intestinal Manipulation

Vilz

Overhaus

Stoffels

et al. 2012

JoVE

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Inflammation of the gastrointestinal tract is a common reason for a variety of human diseases. Animal research models are critical in investigating the complex cellular and molecular of intestinal pathology. Although the tunica mucosa is often the organ of interest in many inflammatory diseases, recent works demonstrated that the muscularis externa (ME) is also a highly immunocompetent organ that harbours a dense network of resident immunocytes.1,2 These works were performed within the standardized model of intestinal manipulation (IM) that leads to inflammation of the bowel wall, mainly limited to the ME. Clinically this inflammation leads to prolonged intestinal dysmotility, known as postoperative ileus (POI) which is a frequent and unavoidable complication after abdominal surgery. 3 The inflammation is characterized by liberation of proinflammatory mediators such as IL-6 4 or IL-1β or inhibitory neurotransmitters like nitric oxide (NO). 5 Subsequently, tremendous numbers of immunocytes extravasate into the ME, dominated by polymorphonuclear neutrophils (PMN) and monocytes and finally maintain POI.2 Lasting for days, this intestinal paralysis leads to an increased risk of aspiration, bacterial translocation and infectious complications up to sepsis and multi organ failure and causes a high economic burden. 6In this manuscript we demonstrate the standardized model of IM and in vivo assessment of gastrointestinal transit (GIT) and colonic transit. Furthermore we demonstrate a method for separation of the ME from the tunica mucosa followed by immunological analysis, which is crucial to distinguish between the inflammatory responses in these both highly immunoactive bowel wall compartments. All analyses are easily transferable to any other research models, affecting gastrointestinal function. Video LinkThe video component of this article can be found at http://www.jove.com/video/4086/ Protocol AnimalsMale C57Bl6/J mice with a mean weight of 25 g were obtained from Harlan Winkelmann (Borchen, Germany). All experiments were performed in accordance with the federal law regarding the protection of animals. The principles of laboratory animal care were followed. Animals were maintained on a 12-hr light/dark cycle and provided with commercially available rodent chow and tap water ad libitum. Animals should be housed at least 7 days after arrival in your animal facility before experiments. Note that all experiments can be easily adapted to rats or other species and with slight modifications into large animal models.

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“…11 A previous work of our group shows by the use of the present methods that immunocytes from intestinally manipulated small bowel disseminate to the unmanipulated colon.…”

Section: Discussionmentioning

confidence: 65%

Functional Assessment of Intestinal Motility and Gut Wall Inflammation in Rodents: Analyses in a Standardized Model of Intestinal Manipulation

Vilz

Overhaus

Stoffels

et al. 2012

JoVE

View full text Add to dashboard Cite

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“…Although the exact causes of postoperative ileus are not fully understood, it has been postulated that an imbalance of sympathetic and parasympathetic inputs to the GI tract results in a reduction in propulsive motility, contributing to or causing signs of ileus [6][7][8]20].…”

Section: Discussionmentioning

confidence: 99%

“…Although other causes have been proposed [1], POI is supposedly caused by surgical manipulation and inflammation [6][7][8]. Many therapies have been proposed to prevent and treat POI in horses [9] but to date none is considered fully effective.…”

Section: Introductionmentioning

confidence: 99%

Effects of Bit Chewing on Right Upper Quadrant Intestinal Sound Frequency in Adult Horses

Giusto

Pagliara

Gandini

2014

Journal of Equine Veterinary Science

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“…It has been shown that inflammatory infiltrates and hypomotility also occur in unmanipulated stomach and colon after standardized jejunal manipulation (72). This propagation of the intestinal inflammation to unmanipulated parts of the gastrointestinal tract has been termed as "gastrointestinal field effect" (FE) (72,83). We also observed FE in rodents after orthotopic small bowel transplantation excluding a spinal or supraspinal reflex (3,80,81).…”

mentioning

confidence: 85%

“…We also observed FE in rodents after orthotopic small bowel transplantation excluding a spinal or supraspinal reflex (3,80,81). In humans, the colonic ileus promotes intraluminal bacterial overgrowth and translocation (4,15,43,49,50,72). Therefore, we intended to investigate the causes for FE in our established rodent model of IM.…”

mentioning

confidence: 99%

Impact of CCR7 on the gastrointestinal field effect

Koscielny

Engel

Maurer

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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.2010.-Standardized intestinal manipulation (IM) leads to local bowel wall inflammation subsequently spreading over the entire gastrointestinal tract. Previously, we demonstrated that this so-called gastrointestinal field effect (FE) is immune mediated. This study aimed to investigate the role of CCR7 in IM-induced FE. Since CCR7 is expressed on activated dendritic cells and T cells and is well known to control their migration, we hypothesized that lack of CCR7 reduces or abolishes FE. Small bowel muscularis and colonic muscularis from CCR7Ϫ/Ϫ and wild-type (WT) mice were obtained after IM of the jejunum or sham operation. FE was analyzed by measuring gastrointestinal transit time of orally given fluorescent dextran (geometric center), colonic transit time, infiltration of MPO-positive cells, and circular smooth muscle contractility. Furthermore, mRNA levels of the inflammatory cytokine IL-6 were determined by RT-PCR. The number of dendritic cells and CD3ϩCD25ϩ T cells separately isolated from jejunum and colon was determined in mice after IM and sham operation. There was no significant difference in IL-6 mRNA upregulation in colonic muscularis between sham-operated WT and CCR7 Ϫ/Ϫ mice after IM. Contractility of circular muscularis strips of the colon was significantly improved in CCR7 Ϫ/Ϫ animals following IM and did not vary significantly from sham-operated animals. Additionally, inflammation of the colon determined by the number of MPO-positive cells and colonic transit time was significantly reduced in CCR7 Ϫ/Ϫ mice. In contrast, jejunal contractility and jejunal inflammation of transgenic mice did not differ significantly from WT mice after IM. These data are supported by a significant increase of CD3ϩCD25ϩ T cells in the colonic muscularis of WT mice after IM, which could not be observed in CCR7Ϫ/Ϫ mice. These data demonstrate that CCR7 is required for FE and postoperative ileus. CCR7 indirectly affects FE by inhibiting migration of activated dendritic cells and of T cells from the jejunum to the colon. These findings support the critical role of the adaptive immune system in FE. postoperative ileus; chemokine receptor 7 POSTOPERATIVE ILEUS (POI) is an inevitable sequela of abdominal surgery or trauma with a variably gradual manifestation. It leads to postoperative discomfort, prolonged hospitalization, and increased patient morbidity and has a high impact on socioeconomic costs (27,43,49,63). The pathophysiology of POI and postoperative gastrointestinal dysmotility, respectively, has been elucidated in recent years. POI is marked by a neurogenic phase and a clinically relevant prolonged inflammatory phase. Both the neuronal activation by intestinal manipulation (IM) and inflammatory cell infiltrates in the intestinal muscularis compromise gastrointestinal motility. These detrimental alterations are emphasized as major factors in the development of POI (4,8,9,15,16,[35][36][37][38][40][41][42]. We reported a time-and trauma-degree-dependent inflammatory cascade (35, 36); infiltration of leukocytes (40 -42...

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Selective jejunal manipulation causes postoperative pan-enteric inflammation and dysmotility

Cited by 158 publications

References 27 publications

Functional Assessment of Intestinal Motility and Gut Wall Inflammation in Rodents: Analyses in a Standardized Model of Intestinal Manipulation

Functional Assessment of Intestinal Motility and Gut Wall Inflammation in Rodents: Analyses in a Standardized Model of Intestinal Manipulation

Effects of Bit Chewing on Right Upper Quadrant Intestinal Sound Frequency in Adult Horses

Impact of CCR7 on the gastrointestinal field effect

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