Inhibition of macrophage function prevents intestinal inflammation and postoperative ileus in rodents

Wehner, Sven; Behrendt, Florian F.; Lyutenski, Boris N.; Lysson, Mariola; Bauer, Anthony J.; Hirner, A.; Kalff, Jörg C.

doi:10.1136/gut.2005.089615

Cited by 213 publications

(245 citation statements)

References 43 publications

(26 reference statements)

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“…We and others showed previously that infection with several different enteric nematodes induced a stereotypic elevation in intestinal smooth muscle responses to acetylcholine, serotonin, agonists of protease-activated receptors, and to nerve stimulation 7,8,14,16,23 . The contribution of macrophages to Th1-mediated changes in smooth muscle contractility is well established 20,24 . To determine the functional role of AAMϕ on N. brasiliensis infection, we used Cl 2 MDP-liposome to deplete macrophages.…”

Section: Discussionmentioning

confidence: 99%

Th2 Cytokine-Induced Alterations in Intestinal Smooth Muscle Function Depend on Alternatively Activated Macrophages

et al. 2008

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Background & Aims-Enteric nematode infection induces a strong Th2 cytokine response and is characterized by increased infiltration of various immune cells including macrophages. The role of these immune cells in host defense against enteric nematode infection, however, remains poorly defined. The present study investigated the role of macrophages and the arginase pathway in nematode-induced changes in intestinal smooth muscle function and worm expulsion.

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Section: Discussionmentioning

confidence: 99%

Th2 Cytokine-Induced Alterations in Intestinal Smooth Muscle Function Depend on Alternatively Activated Macrophages

et al. 2008

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“…Gastrointestinal transit was measured in sham-operated and manipulated animals at 25.5 h after surgical procedure (n ϭ 10 each group) as described previously (40,72,87). Twenty-four hours after surgical procedure, animals underwent light anesthesia and were given fluorescent-labeled dextran (molecular weight 70,000; Sigma-Aldrich) via gavage into the stomach.…”

Section: Functional Studiesmentioning

confidence: 99%

“…Total RNA was analyzed in muscularis externa specimen that was prepared and reverse transcribed to complementary DNA (cDNA) as described before (87). In brief, total RNA extraction was performed using a RNA extraction kit (Macherey & Nagel, Düren, Germany) and contaminating DNA was eliminated from the RNA preparations using Ambion DNA-free solution (Ambion, Huntingdon, UK).…”

Section: Real-time Rt-pcrmentioning

confidence: 99%

“…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, 72, 83), macrophages (21,22,37,87), and immunologically competent cells (35,36,40,67,69,72,81,83); and an upregulation of proinflammatory cytokines within the intestinal muscularis (36, 38 -40, 66, 68, 71, 80 -82, 84, 88). The pharmacological or genetic inhibition of macrophages ameliorated the POI in rodents (87, 89).…”

mentioning

confidence: 99%

“…We reported a time-and trauma-degree-dependent inflammatory cascade (35,36); infiltration of leukocytes (40 -42, 72, 83), macrophages (21,22,37,87), and immunologically competent cells (35,36,40,67,69,72,81,83); and an upregulation of proinflammatory cytokines within the intestinal muscularis (36, 38 -40, 66, 68, 71, 80 -82, 84, 88). The pharmacological or genetic inhibition of macrophages ameliorated the POI in rodents (87,89). It has been shown that inflammatory infiltrates and hypomotility also occur in unmanipulated stomach and colon after standardized jejunal manipulation (72).…”

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confidence: 99%

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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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Natural Helicobacter infection modulates mouse intestinal muscularis macrophage responses

Hoffman

Fleming

2010

Cell Biochemistry & Function

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Helicobacter species are common laboratory pathogens which induce intestinal inflammation and disease in susceptible mice. Since in vitro studies indicate that Helicobacter products activate macrophages, we hypothesized that in vivo Helicobacter infection regulates the inflammatory response of intestinal muscularis macrophages from C57Bl/6 mice. Helicobacter hepaticus infection increased surface expression of macrophage markers F4/80, CD11b, and MHC-II within whole intestinal muscle mounts. However, constitutive cytokine and chemokine production by macrophages isolated from infected mice significantly decreased compared to macrophages from uninfected mice despite no detectable bacterial products in the cultures. In addition, muscularis macrophages from infected mice up-regulated FIZZ-1 and SK-1 gene expression, suggesting the macrophages had an anti-inflammatory phenotype. Corresponding with increased anti-inflammatory gene expression, macrophages from infected mice were more phagocytic but did not produce cytokines after stimulation with LPS and IFN-γ or immune complexes and IL-4. Therefore, the presence of Helicobacter infection matures intestinal muscularis macrophages, modulating the constitutive macrophage response to become more antiinflammatory and resistant to secondary stimulation.

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Inhibition of macrophage function prevents intestinal inflammation and postoperative ileus in rodents

Abstract: Resident intestinal muscularis macrophages are initially involved in inflammatory responses resulting in postoperative ileus. Depletion and inactivation of the muscularis macrophage network prevents postoperative ileus.

Cited by 213 publications

References 43 publications

Th2 Cytokine-Induced Alterations in Intestinal Smooth Muscle Function Depend on Alternatively Activated Macrophages

Th2 Cytokine-Induced Alterations in Intestinal Smooth Muscle Function Depend on Alternatively Activated Macrophages

Impact of CCR7 on the gastrointestinal field effect

Natural Helicobacter infection modulates mouse intestinal muscularis macrophage responses

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