Upregulated expression of substance P in basophils of the patients with chronic spontaneous urticaria: induction of histamine release and basophil accumulation by substance P
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Human basophils have been implicated in the pathogenesis of chronic spontaneous urticaria (CSU), and substance P (SP) is a possible candidate as histamine-releasing factor in some patients with CSU. However, little is known of relationship between basophils and SP in CSU. In the present study, we investigated expression of SP and NK1R on basophils from patients with CSU, and influence of SP on basophil functions by using flow cytometry analysis, basophil challenge, and mouse sensitization model techniques. The results showed that plasma SP level and basophil numbers in CSU patients were higher than that in HC subject. The percentages of SP+ and NK1R+ basophils were markedly elevated in CSU blood in comparison with HC blood. Once added, SP induced up to 41.2 % net histamine release from basophils of CSU patients, which was comparable with that provoked by anti-IgE, and fMLP. It appeared that SP induced dramatic increase in blood basophil numbers of mice following peritoneal injection. Ovalbumin (OVA)-sensitized mice had much more SP+ and NK1R+ basophils in blood than non-sensitized mice. In conclusion, the elevated plasma concentration of SP, upregulated expression of SP and NK1R on basophils, and the ability of SP in induction of basophil degranulation and accumulation indicate strongly that SP is most likely a potent proinflammatory mediator, which contributes greatly to the pathogenesis of CSU through basophils. Inhibitors of SP and blockers of NK1R are likely useful agents for treatment of CSU.
KeywordsAnti-IgE Basophil NK1R Substance P TSLP
Chronic spontaneous urticaria
Mean fluorescence intensity
This project was sponsored by the grants from the “12th Five-Year” National Science and Technology Supporting Plan (2014BAI07B02), the National Natural Science Foundation of China (nos. 81172836, 81471592, and 81472016), Major Science and Technology Platform for Institution of Higher Education in Liaoning province (2014168), and the National Natural Science Foundation of Liaoning Province (2014022027, 2014022019). Program for Liaoning Innovation Research Team in Universities (LNIRT, LT2013017), Climbing Scholar Project for Institution of Higher Education in Liaoning province (2013222), Allergic Disease Translational Medicine Research Center of Liaoning Province (201341), Liaoning Provincial Engineering Research Center for Diagnosing & Treating Inflammatory Disease (20141093), Clinical Capability Construction Project for Liaoning Provincial Hospitals (LNCCC-A06-2014), and “12th Five-Year” public welfare industry special scientific research project (2015SQ00136).
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