Vagus Nerve Activity Augments Intestinal Macrophage Phagocytosis via Nicotinic Acetylcholine Receptor alpha 4 beta 2
| Autor: | Susanne A. Snoek, Siamon Gordon, Maikel P. Peppelenbosch, Caroline Verseijden, Guy E. Boeckxstaens, Wouter J. de Jonge, David R. Greaves, Oana I. Stanisor, Esmerij P. van der Zanden, Sigrid E.M. Heinsbroek |
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| Přispěvatelé: | Other departments, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Gastroenterology and Hepatology, Tytgat Institute for Liver and Intestinal Research, Extramural researchers |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Phagocytic cup
Male STIMULATION medicine.medical_specialty Nicotine medicine.medical_treatment Biology Cholinergic Agonists In Vitro Techniques Receptors Nicotinic PATHWAY ACTIVATION Dynamin II Mice Intestinal mucosa Phagocytosis INFLAMMATION Internal medicine medicine Animals Intestinal Mucosa NEONATAL MATERNAL SEPARATION ALVEOLAR MACROPHAGES Cells Cultured Mice Knockout Mice Inbred BALB C Hepatology Macrophages Gastroenterology Vagus Nerve BACTERIAL CLEARANCE Acetylcholine Endocytosis Vagus nerve Cell biology Mice Inbred C57BL Nicotinic acetylcholine receptor Nicotinic agonist Endocrinology nervous system BARRIER FUNCTION SUBUNIT Macrophage cytokine production Macrophages Peritoneal Vagus nerve stimulation medicine.drug VAGAL NERVE |
| Zdroj: | Gastroenterology, 137(3). W.B. Saunders Ltd Gastroenterology, 137(3), 1029-1039. W B SAUNDERS CO-ELSEVIER INC |
| ISSN: | 0016-5085 |
| Popis: | BACKGROUND & AIMS: The vagus nerve negatively regulates macrophage cytokine production via the release of acetylcholine (ACh) and activation of nicotinic acetylcholine receptors (nAChR). In various models of intestinal inflammation, vagus nerve efferent stimulation ameliorates disease. Given the actively constrained cytokine responses of intestinal macrophages, we explored the effect of nAChR activation on endocytosis and phagocytosis by macrophages residing in the peritoneal and mucosal compartment. METHODS: The phagocytic uptake by intestinal and peritoneal macrophages was measured by fluorescence-activated cell sorter analysis, and the nAChR involved was determined by pharmacologic blockade, short hairpin RNA-assisted gene knockdown, and the use of specific nAChR knockout mice. The effect of electrical vagus nerve stimulation on epithelial translocation and macrophage uptake of lummal particles was studied in mice. RESULTS: In isolated intestinal and peritoneal macrophages, nAChR activation enhanced endocytosis and phagocytosis. This effect was mediated via stimulated. recruitment of GTPase Dynamin-2 to the forming phagocytic Cup. These effects involve nAChR alpha 4/beta 2, rather than nAChR alpha 7. Despite enhanced bacterial uptake, acetylcholine reduced NF-kappa B activation and pro-inflammatory cytokine production, while stimulating anti-inflammatory interleukin-10 production. Vagus nerve stimulation in mice altered mucosal immune responses by augmenting epithelial transport and uptake of luminal bacteria by lamina propria macrophages. CONCLUSIONS: ACh enhances phagocytic potential while inhibiting immune reactivity via nAChR alpha 4/beta 2 in mouse macrophages. Hence, vagus nerve efferent activity may stimulate surveillance in the intestinal mucosa and peritoneal compartment. |
| Databáze: | OpenAIRE |
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