Substance P-Induced Histamine Release in Human Cutaneous Mast Cells

Ebertz, J. Mark; Hirshman, Carol A.; Kettelkamp, Nancy; Uno, Hideo; Hanifin, Jon M.

doi:10.1111/1523-1747.ep12470339

Cited by 110 publications

(39 citation statements)

References 34 publications

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“…The time course of neuropeptide-induced histamine release from skin mast cells is rapid, being complete within 30s. This is much faster than substance P-induced histamine release demonstrable in vitro from human skin slices where physical barriers to diffusion of both peptide and histamine may give a false time course of mast cell activation (Ebertz et al, 1987). Removal of extracellular calcium reduces substance P-induced histamine release by < 50% and has little effect on histamine release induced by VIP or somatostatin, indicating that these secretagogues may activate secretion either by mobilization of intracellular calcium or by a calcium-independent mechanism.…”

Section: Discussionmentioning

confidence: 88%

Characterization of neuropeptide‐induced histamine release from human dispersed skin mast cells

Lowman

Benyon

Church

1988

British J Pharmacology

199

103

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1 Human skin mast cells, unlike other human mast cells so far studied, released histamine in a concentration-related manner in response to substance P, vasoactive intestinal peptide (VIP) and somatostatin (1 yM to 30 yM). In contrast, eledoisin, physalaemin, neurokinin A, neurokinin B, calcitonin gene-related peptide (CGRP), neurotensin, bradykinin and Lys-bradykinin induced negligible histamine release. 2 The low histamine releasing activity of physalaemin, eledoisin, neurokinin A and neurokinin B relative to substance P suggests that the human skin mast cell activation site is distinct from the tachykinin NK-1, NK-2 or NK-3 receptors described in smooth muscle.3 The relative potencies of substance P and its fragments SP2 11, SP3 11, SP4_11 and SP1,4 in releasing histamine from human skin mast cells suggests that both the basic N-terminal amino acids and the lipophilic C-terminal portion of substance P are essential for activity. 4 Peptide-induced histamine release, like that induced by compound 48/80, morphine and poly-Llysine, is rapid, reaching completion in 10-20s, is largely independent of extracellular calcium but requires intact glycolysis and oxidative phosphorylation. The substance P analogue, [D-Pro4,D-Trp7'9 "0] SP411 (SPA), not only reduced substance Pinduced histamine release in a concentration-related manner but also inhibited that induced by VIP, somatostatin, compound 48/80, poly-L-lysine and morphine but not anti-IgE. 6 The similar characteristics of histamine release induced by substance P. VIP, somatostatin, compound 48/80, poly-L-lysine and morphine suggest that they share a common pathway of activationsecretion coupling distinct from that of IgE-dependent activation. Furthermore, the ability of human skin mast cells to respond to basic non-immunological stimuli including neuropeptides may reflect a specialised function for these cells.

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Section: Discussionmentioning

confidence: 88%

Characterization of neuropeptide‐induced histamine release from human dispersed skin mast cells

Lowman

Benyon

Church

1988

British J Pharmacology

199

103

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“…Although mast cells express SP receptors, their involvement in neurogenic inflammation has been debated. Neuropeptides can induce histamine release in a number of tissues (12,13,23,29), but it has been questioned whether endogenously released neuropeptides are present in sufficient amounts to induce mast cell activation and subsequent histamine release in human skin (22,32,40).…”

Section: Discussionmentioning

confidence: 99%

Lowering of interstitial fluid pressure after neurogenic inflammation in mouse skin is partly dependent on mast cells

Karlsen¹,

Bletsa²,

Gjerde³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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Neurogenic inflammation is known to induce lowering of interstitial fluid pressure (P if) in mouse skin. This study examined the possible role of mast cell activation secondary to neuropeptide release in lowering of P if by using , and neurokinin A, from the capsaicin-sensitive nerve endings. Capsaicin releases neuropeptides through binding to the vanilloid receptor subtype 1 (VR1) (9), which in turn induces an inflammatory response in various tissues of both rodents and humans (2, 21). This response is characterized by increased arteriolar vasodilatation and protein extravasation due to increased permeability of the postcapillary venules resulting in fluid accumulation in the tissue. Previous reports from our research group have shown that the response in the initial phase of neurogenic inflammation involves lowering of interstitial fluid pressure (P if ) as observed both in rat trachea (16) and mouse skin (25). P if is important in tissue fluid homeostasis both in the regulation of fluid filtration across the capillary and as the filling pressure for the lymphatics (1). In contrast to the classic view of P if serving as an edema-preventing mechanism, P if has been shown to play an active part in the initial phase of edema in a number of inflammatory models with a lowering of P if to more negative values (16,31,34,35). According to Starling's hypothesis, this lowering of P if will increase net filtration pressure across the capillary and hence contribute to fluid accumulation in the interstitial space.Mast cells have been thought of as possible participants in the neurogenic inflammatory response because they contain numerous inflammatory mediators and are localized in close proximity to the capsaicin-sensitive nerve endings (37,39). Alterations in the number of SP-reactive fibers and mast cell-nerve contacts have been reported as parts of the pathology of several diseases (3,19,45). SP can activate mast cells both through binding of the neurokinin-1 receptor present on these cells (8) and through receptor-independent mechanisms (10). The significance of mast cell activation as a part of neurogenic inflammation has been questioned in a number of studies, and the results are yet not conclusive. Supporting the involvement of mast cells are the findings that stimulation of the rat saphenous nerve induces mast cell degranulation (27) and that SP in high concentrations (40) as well as topical application of capsaicin (7) induce cutaneous mast cell degranulation in human forearm. In contrast, Petersen et al. (32) detected no release of SP and histamine after capsaicin injection in the same area.In light of the knowledge that capsaicin-sensitive nerve endings are localized close to connective tissue mast cells (CTMCs) in mouse skin (6) and that mast cell activation by compound 48/80 (C48/80) induces a lowering of P if in skin of both rats and mice (20,25,36), the question arises as to whether mast cells are involved in the events leading to lowering of P if in neurogenic inflammation. In a recent study (25) we exami...

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“…Kieman demonstrated that antidromic electrical stimulation (ES)' of sensory nerves induces cutaneous vasodilation and augmented vascular permeability, and also results in degranulation of cutaneous mast cells (1,2). Several different neuropeptides which can induce alterations in vascular tone and/or permeability when injected in vivo can also stimulate degranulation of a variety ofhuman and rodent mast cell populations in vitro or in vivo (reviewed in [3][4][5][6][7][8][9][10][11][12][13][14][15][16]. Cutaneous mast cells are particularly sensitive to stimulation by substance P (4, 5-8, 10-12, 15, 16), which can induce a wheal and flare response when injected into the skin in doses as low as 10 pmol (4)(5)(6)(7)(8)11).…”

Section: Introductionmentioning

confidence: 99%

Substance P-induced augmentation of cutaneous vascular permeability and granulocyte infiltration in mice is mast cell dependent.

Yano

Wershil²,

Arizono³

et al. 1989

J. Clin. Invest.

179

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The undecapeptide substance P is thought to mediate both vasodilatation and augmented vascular permeability when released from sensory nerve endings in the skin. Substance P also induces mast cell degranulation in vitro or in vivo. However, the extent to which substance P-induced changes in vascular permeability are mast cell-dependent is unclear. We investigated this issue by injecting substance P and certain related peptides (substance P,I4, substance P4.11) into the skin of genetically mast cell-deficient WBB6F,-W/W' or WCB6F1-SI/Sid mice, the congenic normal (+/+) mice, and WIW' mice which had undergone selective local repair of their mast cell deficiency by intradermal injection of IL-3-dependent mast cells generated in vitro from the bone marrow cells of the congenic +/+ mice. Substance P induced significant augmentation of vascular permeability and significant cutaneous swelling when injected into normal mice at doses as low as 2 pmol i.d. Substance P also induced granulocyte infiltration, although the infiltrates were modest and were seen at doses of peptide from 5 to more than 20-fold higher than those required for induction of tissue swelling. The effects of substance P on tissue swelling, vascular permeability, and granulocyte infiltration were virtually entirely mast cell dependent. By contrast, substance P-4 was inactive in our assays at 25 nmol/site, and substance P4.11 induced modest augmentation of vascular permeability, which was at least in part mast cell independent.

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Substance P-Induced Histamine Release in Human Cutaneous Mast Cells

Cited by 110 publications

References 34 publications

Characterization of neuropeptide‐induced histamine release from human dispersed skin mast cells

Characterization of neuropeptide‐induced histamine release from human dispersed skin mast cells

Lowering of interstitial fluid pressure after neurogenic inflammation in mouse skin is partly dependent on mast cells

Substance P-induced augmentation of cutaneous vascular permeability and granulocyte infiltration in mice is mast cell dependent.

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