Natural killer cell functions mediated by the neuropeptide substance P.
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.
Feistritzer
Clemens
C
Intensive Care Unit, Division of General Internal Medicine, Department of Internal Medicine, Faculty of Medicine, University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria.
Clausen
Johannes
J
Sturn
Daniel H
DH
Djanani
Angela
A
Gunsilius
Eberhard
E
Wiedermann
Christian J
CJ
Kähler
Christian M
CM
D002633:Chemotaxis / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D015288:Neurokinin A / Q000235:genetics; D064729:Neurokinin-1 Receptor Antagonists; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D013373:Substance P / Q000494:pharmacology*
D064729:Neurokinin-1 Receptor Antagonists; D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D013373:Substance P; D015288:Neurokinin A