Differential role of neurokinin receptors in human lymphocyte and monocyte chemotaxis.
The precise nature of neurokin receptor involvement in human immune cell chemotaxis is unclear. This study therefore sought to directly compare the chemotactic effects of neurokinins on human T lymphocytes and monocytes. Substance P was found to have a similar dose-dependent chemotactic action on T lymphocyte and monocyte populations. In contrast, T lymphocytes were found to be more responsive than monocytes both to the highly selective NK-1 agonist, [Sar(9)Met O(2)(11)]-substance P, and also to the NK-2 selective agonist, beta-alanine neurokinin A((4-10)). Consistent with these findings, substance P-induced chemotaxis of both T lymphocyte and monocytes was attenuated by the selective NK-1 antagonist LY303870. However, the selective NK-2 antagonist MEN 10,376 was only effective in inhibiting the T lymphocyte response. The study confirms that neurokinins have chemotactic actions on immune cells and indicates important functional differences between human T lymphocyte and monocyte responses. This provides a potential mechanism by which the nervous system can selectively influence cellular recruitment in inflammatory disease.
Hood
V C
VC
William Harvey Research Institute, St Bartholomew's & Royal London School of Medicine, Charterhouse Square, EC1M 6BQ, London, UK.
Cruwys
S C
SC
Urban
L
L
Kidd
B L
BL
D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D015288:Neurokinin A / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D018040:Receptors, Neurokinin-1 / Q000819:agonists / Q000378:metabolism*; D018041:Receptors, Neurokinin-2 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D013373:Substance P / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*
C096759:1-(N-(2-methoxybenzyl)acetylamino)-3-(1H-indol-3-yl)-2-(N-(2-(4-(piperidin-1-yl)piperidin-1-yl)acetyl)amino)propane; D007211:Indoles; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments; D010880:Piperidines; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; C064218:neurokinin A (4-10), beta-Ala(8)-; C069192:neurokinin A(4-10), Tyr(5)-Trp(6,8,9)-Lys(10)-; D013373:Substance P; D015288:Neurokinin A