Sensory neuropeptides are potent chemoattractants for human basophils in vitro.
The sensory neuropeptides secretoneurin (SN) and substance P (SP) are involved in "neurogenic" inflammatory processes as they occur in bronchial asthma or allergic rhinitis. A possible interaction with basophils has not been reported to date. Basophils were isolated from healthy donors by magnetic cell sorting technique and migration was explored using Boyden microchemotaxis chambers. SN [10(-8)M] and SP [10(-6) to 10(-8)M] proved to be chemoattractants equally potent to FMLP [10(-8)M] or LPS [10 pg/ml]. Specific anti-SN antibodies and a trypsinization preparation of SN were used to determine the specificity of the SN effect on basophils. The preincubation of basophils with neurokinin-1 (NK-1) or -2 (NK-2) receptor antagonists revealed the SP effect to act via NK-1 receptors in basophils. In addition, we were able to show phosphodiesterases and phosphoinositide-3 kinases to be engaged in the downstream signalling pathway. Our observations reveal for the first time a link between basophils, which are engaged in allergic processes, and the neuropeptides SN and SP. Furthermore, our data might suggest phosphodiesterases or phosphoinositide-3 kinases to be new therapeutic targets for the treatment of allergic diseases such as asthma or allergic rhinitis.
Cima
Katharina
K
Pneumology, Internal Medicine I, Department of Internal Medicine, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
Vogelsinger
Helene
H
Kähler
Christian M
CM
D001491:Basophils / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D002465:Cell Movement; D002478:Cells, Cultured; D002630:Chemotactic Factors; D006801:Humans; D009479:Neuropeptides / Q000378:metabolism / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D053381:Secretogranin II / Q000378:metabolism / Q000494:pharmacology*; D015398:Signal Transduction; D013373:Substance P / Q000378:metabolism / Q000494:pharmacology*
D002630:Chemotactic Factors; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D053381:Secretogranin II; C081159:secretoneurin; D013373:Substance P