Upregulated expression of substance P in basophils of the patients with chronic spontaneous urticaria: induction of histamine release and basophil accumulation by substance P

Abstract

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.

The role and relevance of mast cells in urticaria

“…23 To be clinically relevant, substance P in particular should be increased in urticaria. Several studies have shown circulating levels of substance P to be higher in CSU patients compared with healthy individuals [111][112][113] although this was not confirmed by another. 114 Furthermore, measurements of substance P and VIP in the skin showed their concentrations to be higher in urticaria patients than in controls.…”

Up-regulated expression of substance P in CD8+ T cells and NK1R on monocytes of atopic dermatitis

“…However, it is difficult to exclude the involvement of other cell types such as basophils in the development of AD as they also express more SP and NK1R upon allergen challenge [13]. …”

“…The SP/NK-1 receptor complex has been recognized as an integral part of the microenvironment of inflammation and is involved in the molecular basis of many human pathologies, [12] including chronic spontaneous urticaria [13] and intestinal fibrogenesis after chronic colitis [14]. However, little is known about the involvement of SP and NK1R in the development of AD.…”

Role of mast cells and basophils in pruritus

“…Substance P (SP), the first member of the tachykinin family of peptides to be identified, and its conventional receptor NK 1 R (neurokinin 1 receptor) are localized with multiple additional neuropeptides in dorsal root ganglia sensory neurons (30%‐50%), basophils, and mast cells . SP‐positive nerve fibers are found in the dermis and epidermis and innervate the dermal vasculature, keratinocytes, dendritic cells, basophils, and mast cells .…”

“…During perennial allergic rhinitis, NK 1 /NK 2 R + mast cells are increased leading to an enhanced association of mast cells with neural projections . Finally, the classical “mast cell disorder” chronic spontaneous urticaria is associated with increased accumulation of SP/NK 1 R + basophils …”