Natural killer cell functions mediated by the neuropeptide substance P
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Updated: Aug 30, 2026

Teasing Out the Interplay Between Natural Killer Cells and Nociceptor Neurons
Published on: June 30, 2022
Clemens Feistritzer1, Johannes Clausen, Daniel H Sturn
1Intensive Care Unit, Division of General Internal Medicine, Department of Internal Medicine, Faculty of Medicine, University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria.
Abstract:
The neuropeptide substance P (SP) can modulate a number of immunological functions in vitro and in vivo. Here, we investigated if SP boosts migration and cytotoxicity of natural killer cells, thus providing a further link between "innate immunity" and neurogenic inflammatory processes like asthma bronchiale. We demonstrate a dose-dependent effect of SP on natural killer cell migration with a maximal response at 10(-8) M SP. SP was shown to stimulate unstimulated as well as interleukin-2 (IL-2)-activated natural killer cells. Stimulation of natural killer cell migration was neurokinin-1 receptor dependent. Furthermore, mRNA encoding the neurokinin-1 receptor was demonstrated as being present in natural killer cells using RT-PCR while mRNA of the neurokinin-2 receptor was not detectable. Additionally, SP seems to influence specific cytotoxicity against Raji and K567 effector cells by a receptor-independent mechanism. In conclusion, our data indicate that functionally active neurokinin-1 receptors can be expressed by human natural killer cells. Substance P might therefore be a novel link between neural structures and innate immunity.
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