Vannucchi, Maria Giuliana

AbstractBackground and AimMuscularis macrophages (MMs) not only mediate the innate immunity, but also functionally interact with cells important for gastrointestinal motility. The aim of this study was to determine the spatial relationship and types of contacts between the MMs and neighboring cells in the muscularis propria of human and mouse stomach, small intestine, and large intestine.MethodsThe distribution and morphology of MMs and their contacts with other cells were investigated by immunohistochemistry and transmission electron microscopy.Key ResultsImmunohistochemistry showed variable shape and number of MMs according to their location in different portions of the muscle coat. By double labeling, a close association between MMs and neighboring cells, that is, neurons, smooth muscle cells, interstitial cells of Cajal (ICCs), telocytes (TCs)/PDGFRα‐positive cells, was seen. Electron microscopy demonstrated that in the muscle layers of both animal species, MMs have similar ultrastructural features and have specialized cell‐to‐cell contacts with smooth muscle cells and TCs/PDGFRα‐positive cells but not with ICCs and enteric neurons.Conclusion & InferencesThis study describes varying patterns of distribution of MMs between different regions of the gut, and reports the presence of distinct and extended cell‐to‐cell contacts between MMs and smooth muscle cells and between MMs and TCs/PDGFRα‐positive cells. In contrast, MMs, although close to ICCs and nerve elements, did not make contact with them. These findings indicate specialized and variable roles for MMs in the modulation of gastrointestinal motility whose significance should be more closely investigated in normal and pathological conditions.

AbstractBackgroundOtilonium bromide (OB) is used as a spasmolytic drug in the treatment of the functional bowel disorder irritable bowel syndrome. Although its acute effects on colonic relaxation are well‐characterized, little is known about the effects of chronic administration ofOBon enteric neurons, neuromuscular transmission, and interstitial cells of Cajal (ICC), key regulators of the gut function.MethodsAdult Sprague–Dawley rats were treated withOBin drinking water at a dose of 2 mg/kg for 30 days. The colons ofOB‐treated and age‐matched control rats were studied by confocal immunohistochemistry to detect immunoreactivity (IR) in myenteric plexus neurons for nitrergic and tachykininergic markers, and also by microelectrode electrophysiology.Key ResultsUsing immunohistochemistry, chronicOBadministration did not change total neuron number, assessed by anti‐HuIR, but resulted in a significant increase inNK1 receptor positive neurons, a decrease in neuronal nitric oxide synthase expressing neurons, and a reduction in volume of substance P in nerve fibers in the myenteric plexus. ChronicOBadministration potentiated inhibitory and excitatory junction potentials evoked by repetitive electrical field stimulation. The various types of colonicICC, detected by KitIR, were not altered nor were slow waves or smooth muscle membrane potential.Conclusions & InferencesChronic treatment withOBcaused significant changes in the nitrergic and tachykinergic components of the myenteric plexus and in both inhibitory and excitatory neurotransmission in the rat colon.