Substance P- and antigen-induced release of leukotriene B 4 , prostaglandin D 2 and histamine from guinea pig skin by different mechanisms in vitro

Abstract

Substance P (SP) induces increased vascular permeability, vasodilatation and granulocyte infiltration upon intradermal injection. Studies with antagonists and mast cell-deficient mice have suggested that granulocyte infiltration in response SP is mediated by leukotriene (LT) B4 derived from mast cells. However, the release of LTB4 has not been detected using mast cells isolated from human skin. Here we report the release of LTB4, prostaglandin (PG) D2 and histamine from guinea pig skin tissue in response to SP. The release of these agents occurred in a dose-dependent manner over a concentration range of SP from 1 x 10(-6) to 3 x 10(-4) M. No detectable PGE2 was released at any concentration up to 3 x 10(-4) M SP. The kinetics of histamine release induced in response to SP was more rapid than that induced by antigen. By comparison, SP-induced and antigen-induced release of LTB4 and PGD2 were similar, but slower than the histamine release. In the absence of extracellular Ca2+, release of histamine and PGD2 in response to SP was partially impaired, but to a lesser extent than that induced by antigen. On the other hand, LTB4 release in response to both SP and antigen was abolished under the same conditions. These results indicate that SP induces the release of LTB4, as well as histamine and PGD2, in the skin most likely from mast cells by a mechanism which may be different from that of mediator release in response to antigen.

Oral lichen planus and neurogenic inflammation: new observations and therapeutic implications from four clinical cases

“…Additionally, mast cells secrete several potent mediators, which may orchestrate neuroinflammation: specifically, substances like histamine, serotonin, and prostaglandins can act directly on specific receptors on sensory nerve endings, while others, like tryptase, activate peripheral nerves by cleaving proteinase‐activated receptors . However stimulated, free nerve terminals release calcitonine gene‐related peptide (CGRP), substance P (SP) and neurokinin‐A, which are vasoactive, pruritogenic, and crucial in central transmission of pain (as mentioned earlier, pruritus and pain may be present in OLP), and may also stimulate mast cells and lymphocytes, leading, in turn, to amplification of inflammatory signals (FIG. , top panel).…”

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“…In mice, SP injections resulted in a dose-dependent increase in scratching of the injected site [12]. The induction of pruritus is due to the SP-induced production of pro-inflammatory cytokines and release of pruritogenic mediators from mast cells such as histamine, tumor necrosis factor (TNF)-α, prostaglandin D2, and leukotriene B4 via binding of SP to NKR1 on keratinocytes and mast cells [13], [19], [20]. The neutralization of these effects by aprepitant most likely suppresses the release of pruritogenic mediators involved in induction and maintenance of chronic pruritus.…”

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“…He had a slight cough , and a wheeze was apparent in his left lower base. A blood 1 Blood cell counts showed white-cell at 6500 ! mm 3 , red-cells at 446 × 10 4 !…”

“…The amount of histamine released to plasma was measured by HPLC. 1 The same test was performed on two normal subjects and two allergy patients (one bronchial asthma, one pollinosis).…”