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. Elsevier 10.1016/j.celrep.2019.05.050

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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, α1- and β2-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 α1-adrenergic agonists increased LV contractility, whereas activation of β2-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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

UniBE Contributor:

Proulx, Steven Thomas

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

2211-1247

Publisher:

Elsevier

Language:

English

Submitter:

Ursula Zingg-Zünd

Date Deposited:

13 Nov 2019 11:36

Last Modified:

13 Nov 2019 11:44

Publisher DOI:

10.1016/j.celrep.2019.05.050

PubMed ID:

31189113

Uncontrolled Keywords:

Ca(2+) imaging autonomic nervous system contractility lymphatic vessels tumor-draining lymphatics

BORIS DOI:

10.7892/boris.134689

URI:

https://boris.unibe.ch/id/eprint/134689

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