Increased number of immunoreactive nerve fibers in atopic dermatitis

Tobin, Desmond J.; Nabarro, G.; Faute, Harold Baart de la; Vloten, W. A. van; Putte, S. C. J. van der; Schuurman, Henk‐Jan

doi:10.1016/0091-6749(92)90134-n

Cited by 205 publications

(160 citation statements)

References 19 publications

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“…9 Similar findings recently have been reported in a model of contact allergy in mice. 7 We therefore assessed the length of nerve fibers in the skin during OX-induced CHS responses.…”

Section: Ox-induced Chs Is Associated With Elongation Of Cutaneous Nesupporting

confidence: 77%

“…First, as noted above, the length of epidermal nerve fibers can be significantly increased in patients with contact eczema 8 or AD, 9 disorders in which mast cells have been implicated. Second, mast cells also are required for optimal expression of certain models of CHS in mice.…”

mentioning

confidence: 99%

“…6 In addition, it has recently been reported that increases in sensory nerve fibers occur in both the epidermis and the dermis in a model of CHS in mice. 7 Moreover, in humans, the length of epidermal nerve fibers can be significantly increased in patients with contact eczema 8 or AD, 9 and increases in both dermal and epidermal nerve fibers have been reported in other dermatological conditions as well, such as prurigo nodularis 10 and notalgia paraesthetica.…”

mentioning

confidence: 99%

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Mast Cell-Derived Tumor Necrosis Factor Can Promote Nerve Fiber Elongation in the Skin during Contact Hypersensitivity in Mice

Kakurai

Monteforte

Suto

et al. 2006

The American Journal of Pathology

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In humans, lesions of contact eczema or atopic dermatitis can exhibit increases in epidermal nerves, but the mechanism resulting in such nerve elongation are not fully understood. We found that contact hypersensitivity reactions to oxazolone in mice were associated with significant increases in the length of nerves in the epidermis and dermis. Using genetically mast cell-deficient c-kit mutant mice selectively repaired of their dermal mast cell deficiency with either wild-type or tumor necrosis factor (TNF)-deficient mast cells, we found that mast cells, and mast cell-derived TNF, significantly contributed to the elongation of epidermal and dermal PGP 9.5 ؉ nerves and dermal CGRP ؉ nerves, as well as to the inflammation observed at sites of contact hypersensitivity in response to oxazolone. Moreover, the percentage of mast cells in close proximity to dermal PGP 9.5 ؉ nerve fibers was significantly higher in wild-type mice and in c-kit mutant mice repaired of their dermal mast cell deficiency by the adoptive transfer of wild-type mast cells than in TNF-deficient mice or in TNF ؊/؊ mast cell-engrafted c-kit mutant mice. These observations show that mast cells, and mast cell-derived TNF, can promote the elongation of cutaneous nerve fibers during contact hypersensitivity in the mouse.

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“…9 Similar findings recently have been reported in a model of contact allergy in mice. 7 We therefore assessed the length of nerve fibers in the skin during OX-induced CHS responses.…”

Section: Ox-induced Chs Is Associated With Elongation Of Cutaneous Nesupporting

confidence: 77%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Mast Cell-Derived Tumor Necrosis Factor Can Promote Nerve Fiber Elongation in the Skin during Contact Hypersensitivity in Mice

Kakurai

Monteforte

Suto

et al. 2006

The American Journal of Pathology

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“…In human atopic dermatitis, scratching the itchy sites was thought to induce serious dermatitis, and it frequently caused hypertrophy of peripheral nerve and hyperplasia of neural fiber bundles (22)(23)(24), leading to a high density of peripheral nerve fibers along with the progress of the disease. This bad cycle might be one of the bases for the refractory atopic skin inflammation (25).…”

Section: Discussionmentioning

confidence: 99%

Refractory Skin Injury in Complex Knock-out Mice Expressing Only the GM3 Ganglioside

Inoue

Fujii

Furukawa

et al. 2002

Journal of Biological Chemistry

108

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We generated double knock-out mice lacking the GM2/ GD2 and the GD3 synthase gene by mating single gene mutants, and we analyzed the abnormal phenotypes of the mutant mice expressing only the GM3 ganglioside. We observed a refractory skin lesion that appeared primarily on the face of the mutant mice at 25 weeks after birth or later. Frequent scratching of the wound sites was observed in mutant mice with the skin injury, suggesting that it is a triggering factor that exacerbates the injury. This was confirmed by isolating mice in special cages for metabolic study in which the skin injury developed more rapidly. Characteristic proliferation of nerve fibers was found in the epidermis and subepidermis at the injured sites of the mutants, probably a result of continuous skin injury. Peripheral nerve degeneration was observed in young mutant mice, suggesting that reduced sensory function induced over-scratching and the resulting skin lesion. The fact that sensory response to mechanical stimuli decreased while that to hot stimuli increased in the mutant mice supports this interpretation. Thus, only GM3-expressing mice displayed the important role of gangliosides in maintaining skin integrity via regulation of the peripheral nerves.Acidic glycosphingolipids, gangliosides, are ubiquitously expressed in the various tissues of vertebrates and play important roles in the regulation of highly organized multicellular systems (1). In particular, they are very much enriched in the nervous system and have been considered to control development, proliferation, differentiation, and maintenance of the neural tissues and cells (2, 3). Expression patterns of various ganglioside species in the nervous system vary during development and are strictly regulated in a spatio-temporal manner (4), suggesting that individual structures of gangliosides contain significant implications for individual situations.A number of studies have been performed to demonstrate the biological function of gangliosides primarily by modifying their structures with enzymes or using inhibitors to block some steps of synthesis (5). Otherwise, the effects of addition of gangliosides to the culture medium or injection into the conditioned animals have been the primary approaches in addressing the significance of gangliosides. However, recent success in the molecular cloning of glycosyltransferase genes brought about an evolutional change in the experimental approaches for carbohydrate function analysis. Availability of glycosyltransferase genes responsible for the synthesis of gangliosides enabled us to remodel ganglioside compositions of cells and tissues in vivo (6, 7) and in vitro (8).Because we isolated GM2/GD2 synthase (EC 2.4.1.92) cDNA (9) and GD3 synthase (EC 2.4.99.8) cDNA (10), we established gene knock-out mice lines of the individual glycosyltransferases. GM2/GD2 synthase gene knock-out mice lacking all complex gangliosides showed almost normal morphogenesis of the nervous system and no definite abnormal behaviors (11), although they showed nerve degene...

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“…In AD, inflammation is related to an elevated skin cell-derived release of nerve growth factor (NGF), leading to an increased density of cutaneous C-fibres (3,4) that might be linked to pruritus (5). Cooling agents, such as menthol or icilin, suppress itch by activating transient receptor potential ion channel M8 (TRPM8) on cutaneous Ad fibres (6,7) and have therefore been used as an antipruritic treatment for many years (8).…”

Section: Introductionmentioning

confidence: 99%

Menthoxypropanediol inhibits nerve growth factor‐induced nerve fibre sprouting in coculture models of sensory neurons and skin cells

Roggenkamp

Worthmann

Sulzberger

et al. 2016

Experimental Dermatology

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Increased number of immunoreactive nerve fibers in atopic dermatitis

Cited by 205 publications

References 19 publications

Mast Cell-Derived Tumor Necrosis Factor Can Promote Nerve Fiber Elongation in the Skin during Contact Hypersensitivity in Mice

Mast Cell-Derived Tumor Necrosis Factor Can Promote Nerve Fiber Elongation in the Skin during Contact Hypersensitivity in Mice

Refractory Skin Injury in Complex Knock-out Mice Expressing Only the GM3 Ganglioside

Menthoxypropanediol inhibits nerve growth factor‐induced nerve fibre sprouting in coculture models of sensory neurons and skin cells

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