Macrophage‐like cells in the muscularis externa of mouse small intestine

Mikkelsen, Hanne B.; Thuneberg, Lars; Rumessen, Jüri Johannes; Thorball, N

doi:10.1002/ar.1092130111

Cited by 82 publications

(89 citation statements)

References 19 publications

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“…Macrophages in the muscle layers of uninfected animals are classified as resident macrophages. 11,15,[23][24][25][26] Although all other immune cells disappeared from the musculature, many macrophages remained 60 days after infection, now concentrated in the AP region and even within the musculature where there were none before infection. Even after 60 days, the macrophages identified by EM were still activated.…”

Section: Discussionmentioning

confidence: 99%

Pathology of Interstitial Cells of Cajal in Relation to Inflammation Revealed by Ultrastructure But Not Immunohistochemistry

Wang

Berezin

Mikkelsen

et al. 2002

The American Journal of Pathology

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The role of interstitial cells of Cajal associated with Auerbach's plexus (ICC-AP) in the pathophysiology of inflammation-induced abnormalities in gut motor activity is poorly understood. Therefore we applied a well-described model of inflammation (infection by Trichinella spiralis) to the mouse small intestine where the structure and function of ICC-AP are best known. Electron microscopic evaluation revealed that 1 to 3 days after infection, selective and patchy damage to the ICC processes occurred, thereby disrupting contacts between these ICC and smooth muscle cells as well as ICC and nerves, which was associated with disordered electrical activity and abnormal peristalsis. Ten to 15 days after infection, damage to ICC-AP was maximal and now involving the cell body and major processes. Our understanding of the role of interstitial cells of Cajal (ICC) in the pathophysiology of intestinal motor disorders related to inflammation is hampered by our limited knowledge of effects of inflammation on this cell system. Therefore, a well-described model of inflammation (infection with T. spiralis) was applied to the mouse small intestine where the structure and function of ICC are best known.ICC associated with Auerbach's plexus (ICC-AP) in the small intestine perform a pacemaker function for intestinal motor activity.1,2 ICC-AP are associated with slowwave-driven peristalsis, which is prominent during gastric emptying and small bowel transit.3 In fact, normal peristaltic activity in the small bowel after gastric emptying of a liquid was absent in W/W v mutant mice that do not have ICC-AP.3 ICC-AP are characterized by elongated cell bodies with extremely long, thin, ramified cell processes interconnected by close apposition contacts and gap junctions. ICC-AP have many ultrastructural features in common with smooth muscle cells and fibroblasts, but can be identified because of a unique combination of ultrastructural features together with unique structural associations with nerves and smooth muscle cells. 4 -6 ICC harbor the c-Kit protein and can therefore be identified at the light microscopy level using immunohistochemistry with c-Kit antibodies. 2,7 In fact, almost all current studies on the pathology of ICC are performed by immunostaining. 8,9 By using both electron microscopy (EM) and immunohistochemistry we discovered in the present study that marked changes in ICC at the EM level, associated with previously observed functional changes, 10 did not lead to any changes at the light microscopy level using Kit immunohistochemistry.

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Section: Discussionmentioning

confidence: 99%

Pathology of Interstitial Cells of Cajal in Relation to Inflammation Revealed by Ultrastructure But Not Immunohistochemistry

Wang

Berezin

Mikkelsen

et al. 2002

The American Journal of Pathology

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“…Recently, the resident macrophages have also been identified in the muscularis externa of the gastro-intestinal (GI) tract. They are regularly distributed in the subserosa and at the level of the myenteric plexus [14]. Resident macrophages at the level of the myenteric plexus are closely come into view not only to myenteric neurons but also proximity to the interstitial cells of Cajal (ICCs), which are considered to be the pacemaker cells in GI tract [15,22,23].…”

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confidence: 99%

Phagocytotic Activation of Muscularis Resident Macrophages Inhibits Smooth Muscle Contraction in Rat Ileum

Sato

Torihashi

Hori

et al. 2007

The Journal of Veterinary Medical Science

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ABSTRACT. Intestinal muscularis resident macrophages distributed in myenteric region may play an important role in the immunological host defense against infection. In this study, we investigated the phagocytic stimulation of resident macrophages on cyclooxygenase-2 (COX-2) expression and smooth muscle contraction in the small intestine of rat. After the injection of FITC-dextran to rat, phagocytosed macrophages could be detected in the myenteric plexus. FITC-positive macrophages were also immunostained with COX-2 antibody. The number of COX-2 immunopositive cells increased in a time-dependent manner reaching its maximum at 4 hr after the injection, which then decreased gradually but considerable number of cells were still remained on 7 days. The injection of FITC-dextran, however, did not change the population of ED2-positive resident macrophages even on 7 days. Production of PGE 2 was significantly higher in the dextran treated tissue as compared to control tissue. In the smooth muscle tissue phagocytosed dextran, carbachol-induced contraction was significantly decreased. The suppression of the carbachol-induced contraction was completely restored by COX inhibitor, indomethacin. Finally we demonstrated that, in freshly isolated macrophage cells, addition of dextran induced a slow and sustained increase in intracellular Ca 2+ concentration. These results indicate that phagocytotic activation of muscularis resident macrophages induces COX-2 gene expression and then results in production of PGE 2 to suppress the smooth muscle contractile activity. KEY WORDS: intestinal smooth muscle, phagocytosis, prostaglandin, resident macrophage.

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“…Elevated IL-1␤ levels are frequently seen in both mucosa and the muscle layer during acute and chronic intestinal inflammation, including inflammatory lesions of patients with forms of inflammatory bowel disease (IBD) such as Crohn's disease and ulcerative colitis (3,4). As for the IL-1␤-producing cells in the intestinal smooth muscle layer during chronic intestinal inflammation, it is attractive to consider resident macrophages, which are regularly distributed with a network structure in the subserosa, at the level of the myenteric plexus, and inside the muscle layer (5)(6)(7).…”

mentioning

confidence: 99%

Chronic Treatment with Interleukin-1β Attenuates Contractions by Decreasing the Activities of CPI-17 and MYPT-1 in Intestinal Smooth Muscle

Ohama

Hori

Sato

et al. 2003

Journal of Biological Chemistry

113

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Interleukin-1␤ (IL-1␤) is a proinflammatory cytokine that plays a central role in inflammatory bowel disease (IBD). In order to elucidate the mechanism of motility disorders frequently observed in IBD, we investigated the long term effects of IL-1␤ on rat ileal smooth muscle contractility by using an organ culture system. When ileal smooth muscle strips were cultured with IL-1␤ (10 ng/ml), contractions elicited by high K ؉ and carbachol were inhibited in a time-dependent manner. IL-1␤ more strongly inhibited the carbachol-induced contractions than high K ؉ with decreasing myosin light chain phosphorylation. In the ␣-toxin-permeabilized ileal muscle, carbachol with GTP or guanosine 5 -3-O-(thio)triphosphate increased the Ca 2؉ sensitivity of contractile elements, and this G protein-coupled Ca 2؉ sensitization was significantly reduced in the IL-1␤-treated ileum. Among the functional proteins involved in the smooth muscle Ca 2؉ sensitization, CPI-17 expression was significantly reduced after the culture with IL-1␤, whereas the expressions of RhoA, ROCK-I, ROCK-II, MYPT-1, myosin light chain kinase, and myosin phosphatase (PP1) were unchanged. The phosphorylation level of CPI-17 by carbachol was low in accordance with the decrease in CPI-17 expression due to IL-1␤ treatment. In contrast, constitutively phosphorylated MYPT-1 was also decreased in the IL-1␤-treated muscles. These results suggest that long term treatment with IL-1␤ decreases either CPI-17 expression or MYPT-1 phosphorylation, which may result in an increase in myosin phosphatase activity to reduce force generation. Based on these findings, we consider IL-1␤ to be an important mediator of gastrointestinal motility disorders in IBD, and CPI-17 and MYPT-1 are key molecules in the decreased smooth muscle contractility due to IL-1␤.

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Macrophage‐like cells in the muscularis externa of mouse small intestine

Cited by 82 publications

References 19 publications

Pathology of Interstitial Cells of Cajal in Relation to Inflammation Revealed by Ultrastructure But Not Immunohistochemistry

Pathology of Interstitial Cells of Cajal in Relation to Inflammation Revealed by Ultrastructure But Not Immunohistochemistry

Phagocytotic Activation of Muscularis Resident Macrophages Inhibits Smooth Muscle Contraction in Rat Ileum

Chronic Treatment with Interleukin-1β Attenuates Contractions by Decreasing the Activities of CPI-17 and MYPT-1 in Intestinal Smooth Muscle

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