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.
Intensive Care Unit, Division of General Internal Medicine, Department of Internal Medicine, Faculty of Medicine, University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria.
Clemens
C
Feistritzer
Johannes
J
Clausen
Daniel H
DH
Sturn
Angela
A
Djanani
Eberhard
E
Gunsilius
Christian J
CJ
Wiedermann
Christian M
CM
Kähler
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