Header

UZH-Logo

Maintenance Infos

A Distinct Role of the Autonomic Nervous System in Modulating the Function of Lymphatic Vessels under Physiological and Tumor-Draining Conditions


Bachmann, Samia B; Gsponer, Denise; Montoya-Zegarra, Javier A; Schneider, Martin; Scholkmann, Felix; Tacconi, Carlotta; Noerrelykke, Simon F; Proulx, Steven T; Detmar, Michael (2019). A Distinct Role of the Autonomic Nervous System in Modulating the Function of Lymphatic Vessels under Physiological and Tumor-Draining Conditions. Cell Reports, 27(11):3305-3314.e13.

Abstract

Lymphatic vessels (LVs) are important in the regulation of tissue fluid homeostasis and the pathogenesis of tumor progression. We investigated the innervation of LVs and the response to agonists and antagonists of the autonomic nervous system in vivo. While skin-draining collecting LVs express muscarinic, α- and β-adrenergic receptors on lymphatic endothelial cells and smooth muscle cells, intestinal lacteals express only β-adrenergic receptors and muscarinic receptors on their smooth muscle cells. Quantitative in vivo near-infrared imaging of the exposed flank-collecting LV revealed that muscarinic and α-adrenergic agonists increased LV contractility, whereas activation of β-adrenergic receptors inhibited contractility and initiated nitric oxide (NO)-dependent vasodilation. Tumor-draining LVs were expanded and showed a higher innervation density and contractility that was reduced by treatment with atropine, phentolamine, and, most potently, isoproterenol. These findings likely have clinical implications given the impact of lymphatic fluid drainage on intratumoral fluid pressure and thus drug delivery.

Abstract

Lymphatic vessels (LVs) are important in the regulation of tissue fluid homeostasis and the pathogenesis of tumor progression. We investigated the innervation of LVs and the response to agonists and antagonists of the autonomic nervous system in vivo. While skin-draining collecting LVs express muscarinic, α- and β-adrenergic receptors on lymphatic endothelial cells and smooth muscle cells, intestinal lacteals express only β-adrenergic receptors and muscarinic receptors on their smooth muscle cells. Quantitative in vivo near-infrared imaging of the exposed flank-collecting LV revealed that muscarinic and α-adrenergic agonists increased LV contractility, whereas activation of β-adrenergic receptors inhibited contractility and initiated nitric oxide (NO)-dependent vasodilation. Tumor-draining LVs were expanded and showed a higher innervation density and contractility that was reduced by treatment with atropine, phentolamine, and, most potently, isoproterenol. These findings likely have clinical implications given the impact of lymphatic fluid drainage on intratumoral fluid pressure and thus drug delivery.

Statistics

Citations

Dimensions.ai Metrics
2 citations in Web of Science®
1 citation in Scopus®
Google Scholar™

Altmetrics

Downloads

26 downloads since deposited on 31 Jul 2019
26 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neonatology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:11 June 2019
Deposited On:31 Jul 2019 10:33
Last Modified:06 Oct 2019 06:01
Publisher:Cell Press (Elsevier)
ISSN:2211-1247
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.celrep.2019.05.050
Official URL:https://www.sciencedirect.com/science/article/pii/S2211124719306795?via%3Dihub
PubMed ID:31189113

Download

Gold Open Access

Download PDF  'A Distinct Role of the Autonomic Nervous System in Modulating the Function of Lymphatic Vessels under Physiological and Tumor-Draining Conditions'.
Preview
Content: Published Version
Filetype: PDF
Size: 4MB
View at publisher
Licence: Creative Commons: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)