Effects of neurokinins on airway and alveolar eosinophil recruitment.
The authors assessed the role of substance P (SP) and neurokinin A (NKA) and their receptor antagonists (RAs) SR140333 and SR48968 (respectively for NK(1) and NK(2) receptors) in pulmonary eosinophil influx induced by stimulation of capsaicin (CAP)-sensitive nerve terminals. The increase in respiratory system resistance after capsaicin infusion was attenuated by NK(2)RA and association of NK(1)NK(2)RA (P<.001). Respiratory system elastance (Ers) increase was attenuated with use of NK(1)NK(2)RA (P<.001). In alveolar wall, there was an increase in eosinophils after 30 minutes of CAP infusion (P<.001) and was attenuated after 24 hours. Pretreatment with NK(1)RA, NK(2)RA, and NK(1)NK(2)RA decreased eosinophils in alveolar wall (P<.001). SP induced an increase of eosinophils in alveolar wall (P<.001), although NKA may also contribute to this response. In airway wall, the authors observed an increase of eosinophils at 30 minutes (P=.006) till 24 hours after CAP infusion. They noticed a predominant influx of cells around airway wall after CAP and SP infusion. Pretreatment with NK(1)RA and NK(1)NK(2)RA reduced eosinophils (P<.001) in airway wall. Both SP and NKA contribute to eosinophil lung recruitment in distal airways and in alveolar wall, and these findings suggest that neurokinins may contribute to the development of eosinophilic inflammation in both allergic asthma and hypersensitivity pneumonitis.
Tibério
Iolanda F L C
IF
Department of Medicine, School of Medicine, University of São Paulo, Brazil.
Leick-Maldonado
Edna A
EA
Miyahara
Leika
L
Kasahara
David I
DI
Spilborghs
Graziela M G T
GM
Martins
Milton A
MA
Saldiva
Paulo H N
PH
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D004804:Eosinophils / Q000166:cytology*; D006168:Guinea Pigs; D008297:Male; D015288:Neurokinin A / Q000494:pharmacology*; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000494:pharmacology; D011014:Pneumonia / Q000276:immunology*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000276:immunology*; D011812:Quinuclidines / Q000494:pharmacology; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D013373:Substance P / Q000494:pharmacology*
D001549:Benzamides; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D011812:Quinuclidines; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; C085215:SR 140333; D013373:Substance P; C073839:SR 48968; D015288:Neurokinin A