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Vagus nerve activity augments intestinal macrophage phagocytosis via nicotinic acetylcholine receptor alpha4beta2.
Gastroenterology. 2009 Sep; 137(3):1029-39, 1039.e1-4.G

Abstract

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 luminal 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 alpha4/beta2, rather than nAChR alpha7. Despite enhanced bacterial uptake, acetylcholine reduced NF-kappaB 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 alpha4/beta2 in mouse macrophages. Hence, vagus nerve efferent activity may stimulate surveillance in the intestinal mucosa and peritoneal compartment.

Authors+Show Affiliations

Department of Gastroenterology and Hepatology, Academic Medical Centre, Amsterdam, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19427310

Citation

van der Zanden, Esmerij P., et al. "Vagus Nerve Activity Augments Intestinal Macrophage Phagocytosis Via Nicotinic Acetylcholine Receptor Alpha4beta2." Gastroenterology, vol. 137, no. 3, 2009, pp. 1029-39, 1039.e1-4.
van der Zanden EP, Snoek SA, Heinsbroek SE, et al. Vagus nerve activity augments intestinal macrophage phagocytosis via nicotinic acetylcholine receptor alpha4beta2. Gastroenterology. 2009;137(3):1029-39, 1039.e1-4.
van der Zanden, E. P., Snoek, S. A., Heinsbroek, S. E., Stanisor, O. I., Verseijden, C., Boeckxstaens, G. E., Peppelenbosch, M. P., Greaves, D. R., Gordon, S., & De Jonge, W. J. (2009). Vagus nerve activity augments intestinal macrophage phagocytosis via nicotinic acetylcholine receptor alpha4beta2. Gastroenterology, 137(3), 1029-39, e1-4. https://doi.org/10.1053/j.gastro.2009.04.057
van der Zanden EP, et al. Vagus Nerve Activity Augments Intestinal Macrophage Phagocytosis Via Nicotinic Acetylcholine Receptor Alpha4beta2. Gastroenterology. 2009;137(3):1029-39, 1039.e1-4. PubMed PMID: 19427310.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vagus nerve activity augments intestinal macrophage phagocytosis via nicotinic acetylcholine receptor alpha4beta2. AU - van der Zanden,Esmerij P, AU - Snoek,Susanne A, AU - Heinsbroek,Sigrid E, AU - Stanisor,Oana I, AU - Verseijden,Caroline, AU - Boeckxstaens,Guy E, AU - Peppelenbosch,Maikel P, AU - Greaves,David R, AU - Gordon,Siamon, AU - De Jonge,Wouter J, Y1 - 2009/05/07/ PY - 2009/01/19/received PY - 2009/04/21/revised PY - 2009/04/27/accepted PY - 2009/5/12/entrez PY - 2009/5/12/pubmed PY - 2009/9/16/medline SP - 1029-39, 1039.e1-4 JF - Gastroenterology JO - Gastroenterology VL - 137 IS - 3 N2 - 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 luminal 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 alpha4/beta2, rather than nAChR alpha7. Despite enhanced bacterial uptake, acetylcholine reduced NF-kappaB 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 alpha4/beta2 in mouse macrophages. Hence, vagus nerve efferent activity may stimulate surveillance in the intestinal mucosa and peritoneal compartment. SN - 1528-0012 UR - https://www.unboundmedicine.com/medline/citation/19427310/Vagus_nerve_activity_augments_intestinal_macrophage_phagocytosis_via_nicotinic_acetylcholine_receptor_alpha4beta2_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0016-5085(09)00737-9 DB - PRIME DP - Unbound Medicine ER -