Mast cells,nerves and neuropeptides in atopic dermatitis and nummular eczema

The association between mast cells and sensory nerves and the distribution of the neuropeptides substance P (SP), vasoactive intestinal polypeptide (VIP) and calcitonin gene-related peptide (CGRP) were studied immunohistochemically in lesional and nonlesional skin of 26 atopic dermatitis (AD) and 23 nonatopic nummular eczema (NE) patients. Mast cell-nerve contacts were counted morphometrically and confirmed by confocal laser scanning microscopy. Neuropeptide positivity was assessed semiquantitatively. Dermal contacts between mast cells and nerves were increased in number in both lesional and nonlesional samples of AD and NE when compared to those in normal controls, although only the values in lesional AD reached statistical significance ( P<0.05). Nerve-mast cell contacts in the basement membrane zone were seen practically only in lesional NE. SP and CGRP fibres were prominently increased in lesional samples when compared to their nonlesional controls both in AD and NE in the epidermis and in the papillary dermis. In both AD and NE, only small differences were found regarding VIP positivity in lesional and nonlesional biopsies. The epidermis was devoid of VIP positivity. In conclusion, SP and CGRP but not VIP fibres were more frequent in lesional than in nonlesional papillary dermis of both AD and NE. Since mast cells are also increased in number in lesions of AD and NE, they are able to maintain neurogenic inflammation through activation by SP and CGRP. The increased SP/CGRP nerves in the epidermis of AD and NE lesions may stimulate keratinocytes to release cytokines which affect various cell types enhancing inflammation.     

Quantitation of tryptase- and chymase-containing mast cells in cutaneous lichen planus.

The distribution and density of tryptase- and chymase-positive mast cells in lesional and non-lesional cutaneous lichen planus (LP) was analysed. For this, enzyme-histochemical staining techniques and morphometrical measurements were applied. In non-lesional LP skin, chymase-positive cells (TC mast cells) showed a distribution similar to that found in both non-lesional psoriatic skin and in normal skin. Tryptase-positive cells (reflecting both T and TC mast cells), however, were increased in number in the upper dermis of non-lesional LP skin. In lesional LP skin, there were fewer chymase-positive cells in the upper dermis, whereas there were more tryptase-positive cells. In the upper dermis, no differences in the number of tryptase containing cells were detected between lesional and nonlesional LP skin. In lesions of LP and psoriasis, tryptase-positive mast cells are increased but differ in their distribution in the papillary dermis. In psoriatic lesions, tryptase-positive cells are frequently observed in epidermal contact, a feature very rarely seen in LP lesions. The present results suggest that the increased numbers of T mast cells in the upper dermis of nonlesional LP skin may be involved in initiating the LP lesion. It seems unlikely that mast cells could be responsible for the epidermal basal cell damage, though T mast cells do participate in the general inflammatory reaction.     

Quantitative enzyme-histochemical analysis of tryptase- and chymase-containing mast cells in psoriatic skin

Summary Tryptase-containing mast cells have recently been found to be increased in the upper dermis of psoriatic lesions. In the present study, the distribution of chymaseand tryptase-containing mast cells was morphometrically analysed at different dermal levels of lesional and non-lesional psoriatic skin (12 patients) as well as normal human skin. Mast cell tryptase was identified enzyme-histochemically, using Z-Gly-Pro-Arg-MNA as the substrate. For demonstrating mast cell chymase, a simple and specific enzyme-histochemical staining method was developed, using Suc-Val-Pro-Phe-MNA as the substrate. All mast cells positive for chymase were also positive for tryptase and Giemsa stain. Although the number of tryptase-positive mast cells was slightly increased throughout the dermis of lesional psoriatic skin, this increase was most pronounced in the upper dermis immediately beneath, and in close contact with, the epidermis. In contrast, the number of chymase-positive mast cells was clearly decreased in the upper dermis of psoriatic lesions, but not in the deeper dermis, as compared with non-lesional psoriatic skin. In addition, all chymase-positive mast cells observed in the upper dermis were very weakly stained when compared with those in the deeper dermis. No differences were found between non-lesional psoriatic skin and normal skin in which the number of mast cells containing chymase was 72–73% of the number containing tryptase. The present results suggest that T mast cells particularly, containing tryptase but no chymase, proliferate in psoriatic lesions, and that the increase in tryptase activity and the decrease in chymase activitiy in the upper dermis may lead to an imbalance in the biochemical regulatory systems.     

Immunohistochemical analysis of sensory nerves and neuropeptides,and their contacts with mast cells in developing and mature psoriatic lesions

The distribution of the neuropeptides substance P (SP), vasoactive intestinal polypeptide (VIP) and calcitonin gene related peptide (CGRP) was studied immunohistochemically in psoriatic skin during the Koebner response (6 h, 2 days, 7 days, 14 days, 21 days), and in mature psoriatic plaques, of 37 psoriatic patients. The morphological association of sensory nerves, SP and VIP with papillary mast cells was also monitored. The nerves containing SP, VIP or CGRP were very scanty in control skin, and in non-lesional and Koebner-negative psoriatic skin. The first psoriatic lesions were seen 7 days after tape stripping the symptomless psoriatic skin. SP- and VIP-containing nerves were slightly increased in Koebner-positive specimens, but the increase was very prominent in dermal papillae of mature psoriatic plaques. In the plaques, nerve-mast cell contacts were significantly increased (p<0.001) compared with non-lesional psoriatic skin. Only SP-positive fibres were detected in the epidermis and in contact with papillary mast cells. VIP was mainly located around capillaries where SP was also found. No change was noted in CGRP-positive fibres between lesional and non-lesional specimens. The appearance of SP and VIP in the capillary walls is morphological evidence for their function as vasodilators in psoriatic lesion. A slight increase in SP- and VIP-positive fibres in Koebner-positive specimens suggests that these neuropeptides may participate in the inflammatory reaction at an early stage. Their prominence in mature psoriatic plaques in turn indicates a role for them in the maintenance of psoriatic lesions. Morphological contacts between mast cells and SP-containing nerves give further evidence to the view that SP is capable of amplifying the inflammatory reaction also through the axon-reflex mechanism.Part of this work was presented at the meeting of the European Society for Dermatological Research, London, UK, 4–7 April 1992     

Intraepidermal nerve fiber expression of calcitonin gene-related peptide, vasoactive intestinal peptide and substance P in psoriasis

In order to evaluate more fully the role of neuropeptides in the pathogenesis of psoriasis, skin biopsies were obtained from 36 patients with psoriasis to identify substance P (SP), vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP). Lesional and nonlesional skin was examined from these biopsies and the results compared with those from biopsies taken from patients with a variety of other inflammatory dermatoses, including lichen planus, lichen simplex chronicus, spongiotic dermatitis, and seborrheic dermatitis. Also studied was a series of nine biopsies taken from patients with no known skin disorders. We found an increase in the number of SP-positive nerve fibers within the epidermis in biopsies from lesional skin of psoriasis patients (8.4 nerves per 3-mm biopsy) compared with nonlesional psoriatic skin (2.6 nerves per 3-mm biopsy) and normal skin (2.0 nerves per 3 mm biopsy). Other inflammatory disorders also demonstrated fewer SP-positive nerves than lesional psoriatic skin; lichen planus (0 nerves per 3 mm biopsy) and lichen simplex chronicus (1.3 nerves per 3 mm biopsy). The difference in SP-positive nerve expression between lesional psoriatic skin and the group comprising nonlesional skin, normal skin, lichen planus, and lichen simplex chronicus attained statistical significance ( P < 0.013). SP-positive intraepidermal nerve fibers in lesional psoriatic specimens were fewer than in spongiotic dermatitis (17.4 nerves per 3 mm biopsy). There was no significant difference in numbers of VIP- or CGRP-immunopositive intraepidermal nerve fibers between psoriatic skin and the group comprising all other material tested. However, in five patients with psoriasis, there was a marked increase in the expression of intraepidermal CGRP (up to 10.7 nerves per 3-mm biopsy) and VIP (up to 8.3 nerves per 3-mm biopsy) which was not observed in control groups. These findings suggest that neuropeptides SP, CGRP, and VIP play a role in the pathogenesis of psoriasis. Received: 3 March 1997     

Detection of transferrin and C3d receptors in the skin of patients with various dermatoses

The localization of transferrin and C3d receptors in various skin lesions and normal appearing skin have been studied on sections with the PAP technique. The transferrin receptor was recognized in the lower epidermis from psoriatic plaques. Here it was more evident than in other inflammatory or hyperproliferative disorders where it was mainly detected on the basal cells. In healthy skin or lesions of lichen planus, scleroderma and ichthyosis the transferrin receptor was not detected in the epidermis. The C3d receptor was in normal skin found on the basement membrane and on elastic fibres in the papillary dermis. The basement membrane was strongly marked in pemphigoid but was not seen in lichen planus and Ehlers-Danlos syndrome. In patients with urticaria factitia, contact dematitis, psoriasis and Darier's disease the suprabasal cells also expressed C3d whereas in other dermatoses the epidermis was negative. Colloid bodies in lichen planus and GVH reactions expressed both the transferrin receptor and C3d.     

Mast cell tryptase and chymase in developing and mature psoriatic lesions

The number and distribution of mast cells in nonlesional and lesional skin samples from 13 psoriatic patients were analyzed enzyme- and immunohistochemically. Mast cell tryptase was stained with the sensitive substrate Z-Gly-Pro-Arg-4-methoxy-2-naphthylamide, and chymase with Suc-Val-Pro-Phe-MNA and monoclonal B7 anti-chymase antibody. In addition, healthy-looking skin from 27 psoriatic patients was tape-stripped resulting in induction of the Köbner response in 9 patients. Sequential biopsies were taken before and after (7, 14 and 21 days) tape-stripping, and both tryptase and chymase were stained enzyme-histochemically. In nonlesional psoriatic skin, 70 ± 24% (mean ± SD) of the mast cells contained chymase enzyme activity, and 78 ± 18% chymase immunoreactivity. About 10% of the chymase-immunoreactive cells lacked chymase activity. In lesional psoriatic skin, tryptase-positive cells were increased in number throughout the dermis but especially beneath the epidermis. Chymase immunoreactivity paralleled the tryptase activity, whereas chymase activity was strongly diminished both in terms of mast cell numbers and in staining intensity in the papillary dermis. The apparent inactivation of chymase may be due to the action of the chymase inhibitors, ₁-antitrypsin and ₁-antichymotrypsin, localized immunohistochemically in mast cells of lesional and nonlesional psoriatic skin. In the developing psoriatic lesion, mast cells displaying chymase activity were already 27–38% decreased in number in the upper dermis on day 7 after tape-stripping, along with the first clinical signs of psoriasis. Earliest alterations in tryptase-positive cells were observed on day 14 as increased mast cell contacts with the epidermis combined with only a slight increase in mast cell numbers in the upper dermis. During the development of a psoriatic lesion, TC mast cells (tryptase⁺, chymase⁺) increase in number in the upper dermis, but chymase becomes inactive at an early stage. The abundant presence of active trypase but inactive chymase in the upper dermis may have a potential role in psoriasis since both of these enzymes can process several biologically active peptides and proteins.     

Skin nerve fibres and their contacts with mast cells in patients with palmoplantar pustulosis

Abstract Patients with palmoplantar pustulosis (PPP) frequently report that stress worsens their condition. A study was therefore made of the distribution and number of nerve fibres positive for protein gene product (PGP) 9.5 (a general nerve marker) and nerve fibres with substance P- and calcitonin gene-related peptide-like immunoreactivity in involved skin from patients with PPP and in skin from healthy controls. The number of mast cells in the papillary dermis was larger (P = 0.0003) in lesional palmar PPP skin than in control skin, and the number of contacts between mast cells and nerve fibres was significantly larger (P = 0.02) in PPP skin than in control skin. Image analysis of the nerve fibres around the sweat glands showed that the positively stained area as a percentage of the total area of the sweat gland (coil + surrounding nerves) was significantly lower in PPP skin (P = 0.0006). Furthermore, the nerves seemed to be fragmented. Neutrophils within and below the pustules and in the papillary dermis showed positive substance P staining. The increased number of contacts between nerves and mast cells in PPP skin and the intense substance P-like immunoreactivity of the neutrophils indicate that neuromediation may influence the inflammation in PPP, whereas the destruction of the nerve fibres around the sweat glands might be a result of the inflammation. Received: 8 October 1999 / Revised: 25 January 2000 / Accepted: 27 January 2000     

细胞分化标志分子在扁平苔藓皮损中异常表达的研究

通过研究扁平苔藓皮损中角质形成细胞分化标志的表达情况，分析扁平苔藓的病理机制。本实验应用免疫组化方法以银屑病和正常皮肤为对照，检测扁平苔藓中TGk、Filaggrin、K17和K16的原位表达。结果显示TGk和Filaggrin在扁平苔藓皮损表皮中表达增强，K17和K16在扁平苔藓皮损表皮中出现阳性染色，银屑病皮损中上述标志分子有类似表达，而正常皮肤中则无此现象。提示扁平苔藓皮损中角质形成细胞存在着过度增生和异常分化，上述增生分化标志可能是其病理改变的分子基础。     

Pruritogenic mediators in psoriasis vulgaris: comparative evaluation of itch-associated cutaneous factors

BACKGROUND: Although some patients with psoriasis vulgaris also complain of severe pruritus, the data available regarding pruritus in psoriasis are sparse. OBJECTIVES: To clarify the mechanism and mediators involved in the pruritus of psoriasis vulgaris, we compared itch-associated factors in lesional skin from psoriatic patients vs. skin without pruritus quantitatively using a panel of histological and immunohistological parameters. PATIENTS AND METHODS: Biopsied specimens were obtained from 38 patients with psoriasis vulgaris who were divided into two groups according to the presence or absence of pruritus. RESULTS: When compared with psoriatic patients devoid of pruritus, lesional skin from patients with pruritus showed the following characteristic features: (i) a rich innervation both in the epidermis and in the papillary dermis; (ii) an increase in neuropeptide substance P-containing nerve fibres in perivascular areas; (iii) decreased expression of neutral endopeptidase in the epidermal basal layer as well as in the endothelia of blood vessels; (iv) many mast cells showing degranulating processes in the papillary dermis; (v) a strong immunoreactivity for nerve growth factor (NGF) throughout the entire epidermis and an increased NGF content in lesional skin homogenates; (vi) an increase in the expression of high-affinity receptors for NGF (Trk A) in basal keratinocytes and in dermal nerves; (vii) an increased population of interleukin-2-immunoreactive lymphocytes; and (viii) a strong expression of E-selectin on vascular endothelial cells. A significant correlation was observed between the severity of pruritus and protein gene product 9.5-immunoreactive intraepidermal nerve fibres, NGF-immunoreactive keratinocytes, expression of Trk A in the epidermis and the density of immunoreactive vessels for E-selectin. These findings indicate that possible pruritogenic mediators in psoriatic lesional skin are neurogenic factors including innervation, neuropeptide substance P, neuropeptide-degrading enzymes and NGF, activated mast cells, one or more cytokines and endothelial-leucocyte adhesion molecules. CONCLUSIONS: These data document for the first time itch-related local markers in psoriasis, and suggest complex and multifactorial mechanisms of pruritus in the disease. These results provide the groundwork for further studies to evaluate the efficacy of antipruritic treatment for psoriatic patients.     

MAST CELL TRYPTASE AND CHYMASE ARE POTENTIAL REGULATORS OF NEUROGENIC INFLAMMATION IN PSORIATIC SKIN

Background. Tryptase and chymase are proteinases present only in mast cells. In psoriatic lesions, mast cells are increased in number. Certain neuropeptides are also more abundant in lesional than nonlesional psoriatic skin. Based on some earlier results as well as the results of the present study, a hypothesis is presented concerning the regulatory action of mast cell tryptase and chymase on neuropeptides in psoriatic inflammation. Methods. Forty patients were biopsied, 13 for a mature psoriatic plaque and 9 patients of 27 for a developing (1–3 weeks) psoriatic lesion induced by tape stripping (Koebner reaction). Each lesion had its nonlesional control from the same patient. Mast cell tryptase and chymase, and the neuropeptides Substance P (SP) vasoactive intestinal polypeptide (VIP), and calcitonin-gene-related peptide (CGRP) were stained by enzyme-and immunohistochemical methods. Morphological contacts between mast cells and neuropeptides were visualized using double stains and quantitated in the upper dermis. Results. As the lesion aged, MCTC mast cells displaying tryptase activity increased in number, whereas chymase activity in these cells decreased. All neuropeptides showed some increase along with the development of the lesion, but SP was most abundant in mature lesions. Substance P-positive nerves had also more contacts with mast cells compared to VIP- or CGRP-containing fibers, the contact count being highest in mature lesions. Conclusions. Tryptase is known to degrade VIP and CGRP, but not SP. Chymase is capable of cleaving both SP and VIP, but is rendered partially inactive in psoriatic skin. These data together with the results of the present study strongly suggest that SP has potency to act as an important mediator in different stages of the psoriatic inflammation.     

Mast cell density in psoriatic skin. The effect of PUVA and corticosteroid therapy

Summary Numbers and volume fractions of mast cells in nonlesional and chronic lesional skin of psoriatic patients were compared with those of normal control skin. Mast cell densities were similar in psoriatic nonlesional and normal control skin. The superficial dermis of lesional psoriatic skin contained more mast cells than either normal or nonlesional psoriatic skin. Neither PUVA nor corticosteroid treatment for 3–4 weeks significantly reduced mast cell numbers or volume fractions in lesional skin, although both treatments clinically and histologically markedly improved the lesions. The results indicate that the initiation of the healing process in psoriatic plaques is not correlated with the mast cell density. The remaining high mast cell density may be normalized later, or after a longer therapy.     

Cellular localization of fractalkine at sites of inflammation: antigen-presenting cells in psoriasis express high levels of fractalkine.

BACKGROUND: Chemokines play a key role in cell trafficking at sites of inflammation. The fractalkine CX3C chemokine is unique in several aspects. Fractalkine is expressed on activated endothelial cells and exists in two forms, either membrane anchored or in a soluble form. The soluble form is a potent chemotactic agent for T cells/monocytes and the anchored form functions as an adhesion molecule. In view of these specific functions fractalkine is capable of controlling the key regulatory mechanisms of cell trafficking at sites of inflammation. OBJECTIVES: Little is known about the significance of this important molecule in inflammatory diseases. We undertook this study to elucidate the role of fractalkine in inflammatory diseases of the skin. METHODS: We used a polyclonal antifractalkine antibody (immunoperoxidase and immunofluorescence stainings) in cryosections obtained from tissues of normal skin and that of selected cutaneous inflammatory diseases (psoriasis, lichen planus, eczema). RESULTS: Increased expression of fractalkine was observed in the dermal blood vessels of lichen planus, eczema and psoriasis tissues. The most striking finding was that the dermal dendrocytes in the papillary dermis of psoriasis tissues expressed high levels of fractalkine. Compared with 186.64 +/- 51.69 fractalkine positive dermal dendrocytes per mm2 of the upper dermis of psoriatic tissue, the number of positive cells in lichen planus, eczema, and normal skin were 17.29 +/- 12.50, 12.50 +/- 6.75 and 5.93 +/- 3.53, respectively. We also performed double label immunofluorescence staining with nerve growth factor receptor (NGF-R) antibody and fractalkine antibody. NGF-R-positive terminal cutaneous nerves were in close contact with the fractalkine-positive dermal dendrocytes in psoriatic lesions. CONCLUSIONS: The results of this study confirm that fractalkine is upregulated at sites of inflammation. Thus, it is likely that this molecule plays a key part in cell trafficking. An increased expression of fractalkine at the dermal papillae provides a plausible explanation for the migration and accumulation of T cells at these sites in psoriasis. Earlier studies have reported an increased number of dermal dendrocytes in psoriatic tissue; however, the functional role of these cells in the pathogenesis of psoriasis is largely unknown. Expression of fractalkine on the surface of dermal dendrocytes suggests an active role for these cells in localization and activation of lesional T cells.     

The role of perforin-mediated apoptosis in lichen planus lesions

Lichen planus is recognized as a T-cell-mediated disease. Histologically, it is characterized by the formation of colloid bodies representing apoptotic keratinocytes. The apoptotic process mediated by CD8⁺ cytotoxic T lymphocytes (CTLs) and NK cells mainly involves two distinct pathways: the perforin/granzyme pathway and the Fas/FasL pathway. So far, little is known regarding the role of perforin-mediated apoptosis in lichen planus. In the present study, the expression and distribution of perforin, T and NK cell subsets in the epidermis and dermis of lesional and nonlesional lichen planus skin were studied. Skin biopsy specimens from lesional and nonlesional skin of ten patients with lichen planus and eight healthy persons were analysed by immunohistochemistry. Significant accumulation of T cells, particularly of CD4⁺ and CD8⁺ subsets, was found in both epidermis and dermis of lichen planus lesions compared with nonlesional and healthy skin. There were no significant differences in the incidence of NK cells (CD16⁺ and CD56⁺) between lesional, nonlesional and healthy skin. Perforin expression was significantly upregulated in the epidermis of lichen planus lesions. In conclusion, accumulation of perforin⁺ cells in the epidermis of lichen planus lesions suggest a potential role of perforin in the apoptosis of basal keratinocytes.     

Lichen planus remission is associated with a decrease of human herpes virus type 7 protein expression in plasmacytoid dendritic cells

The cause of lichen planus is still unknown. Previously we showed human herpes virus 7 (HHV-7) DNA and proteins in lesional lichen planus skin, and significantly less in non-lesional lichen planus, psoriasis or healthy skin. Remarkably, lesional lichen planus skin was infiltrated with plasmacytoid dendritic cells. If HHV-7 is associated with lichen planus, then HHV-7 replication would reduce upon lichen planus remission. HHV-7 DNA detection was performed by nested PCR and HHV-7 protein by immunohistochemistry on lesional skin biopsies from lichen planus patients before treatment and after remission. Biopsies were obtained from lichen planus lesions before treatment (n = 18 patients) and after remission (n = 13). Before treatment 61% biopsies contained HHV-7 DNA versus 8% after remission (P = 0.01). HHV-7-protein positive cell numbers diminished significantly after remission in both dermis and epidermis. Expression of HHV-7 was mainly detected in BDCA-2 positive plasmacytoid dendritic cells rather than CD-3 positive lymphocytes. HHV-7 replicates in plasmacytoid dendritic cells in lesional lichen planus skin and diminishes after remission. This study further supports our hypothesis that HHV-7 is associated with lichen planus pathogenesis.     

血管内皮生长因子在扁平苔藓及银屑病皮损中的表达

目的探讨扁平苔藓及银屑病患者皮损表皮血管内皮生长因子(VEGF)表达情况。方法用抗VEGF及CD34抗体行免疫组化染色,对扁平苔藓及银屑病皮损标本进行观察,计数表皮下方真皮的毛细血管密度。结果正常人表皮VEGF基本阴性,扁平苔藓及银屑病患者非病变部VEGF阴性,移行部表皮上层VEGF染色逐渐由弱到强,由间断到连续;病变部表皮VEGF阳性,以表皮上层细胞质的细颗粒状染色为主。CD34染色各部分真皮上层毛细血管密度为;扁平苔藓的非病变部(45.61±15.70)个/mm²、移行部(68.63±15.36)个/mm²、病变部(92.07±16.84)个/mm²;银屑病的非病变部(43.73±14.55)个/mm²、移行部(72.12±18.81)个/mm²、病变部(100.29±21.93)个/mm²,各病种三个部位之间比较差异均有统计学意义。结论扁平苔藓及银屑病皮损表皮分泌VEGF,并与真皮毛细血管增生扩张密切相关。     

Neuropeptides and general neuronal marker in psoriasis an immunohistochemical study

Nerve fibres immunoreactive to antibodies to vasoactive intestinal polypeptide (VIP) and substance P (SP) were increased in lesional psoriatic skin when assessed semi-quantitatively. Biopsies from psoriatic plaques on the arm were studied in 13 patients and compared with biopsies from non-lesional areas (in three of the same psoriatic subjects) and from normal skin in seven non-psomtic controls. Immunohistochemical methods were used on cryocut skin sections to demonstrate the neuropeptides SP, VIP, calcitonin gene-related peptide and neuropeptide Y, and the general neuronal marker protein gene product (PGP) 9.5. The immunofluorescence was examined by semiquantitative and, for PGP 9.5, by quantitative methods. VIP reactive nerve fibres were increased at areas of eccrine sweat glands throughout the dermis, at the dermo-epidermal junction, and in the epidermis, in psoriasis lesional skin. SP reactive nerve fibres were increased at the dermo-epidermal junction, where the nerves ran parallel with and perpendicularly through the junction. PGP 9.5 reactive nerve fibres showed an increase at the dermo-epidermal junction, in the papillary dermis, and at the eccrine sweat glands in lesional psoriatic skin but not in non-lesional, or in control skin. These findings support the hypothesis that neuropeptides may be involved in the pathogenesis of psoriasis.     

Quantification of cutaneous sensory nerves and their substance P content in psoriasis

The aim of the present study was to extend our previous hypothesis that the inflammatory reaction in psoriasis is neurogenic, and that substance P mediates the inflammation. For this purpose, the pattern of neurofilament-positive sensory nerve fibers was studied and the lengths and substance P content of these fibers measured morphometrically in dermal and epidermal compartments of the psoriatic lesion, psoriatic but lesion-free skin, and control skin. The epidermis and dermis of the psoriatic lesions were significantly more densely innervated with neurofilament-positive fibers than either lesion-free psoriatic or control skin. Although substance P is known to be rapidly degraded in tissues, and its actual concentrations in the sections were unknown, there was an increase in substance P containing nerves in the psoriatic lesion, the increase being significant in the epidermal nerve fibers. No significant differences in the measured parameters were obtained between lesion-free psoriatic and control skin. These results indicate that there is an altered pattern of sensory nerves in a psoriatic plaque and that substance P may be an important mediator in the inflammatory processes that contribute either to the initiation or maintenance of a psoriatic lesion.     

寻常性银屑病皮损处神经纤维的数量及其与朗格汉斯细胞关系的观察

目的 观察寻常性银屑病患者皮损处神经纤维的数量变化及其与朗格汉斯细胞的关系.方法采用免疫组化过氧化物酶法观察28例寻常性银屑病患者皮损处神经纤维的数量变化;采用免疫荧光双标记及共聚焦激光扫描显微镜技术观察寻常性银屑病患者皮损处神经纤维与朗格汉斯细胞的关系.结果寻常性银屑病患者皮损处神经纤维长度显著增加,与正常人对照比较有统计学差异(t=4.09,P＜0.001).皮损表皮内神经纤维与朗格汉斯细胞的接触明显增多,与正常人对照比较有统计学差异(t=3.55,P＜0.01).结论寻常性银屑病皮损处神经纤维长度显著增加,表明此部位神经纤维增生明显,并且表皮内神经纤维与朗格汉斯细胞的直接接触明显增加,提示银屑病患者神经系统的免疫调控作用可能是通过改变朗格汉斯细胞的功能实现的。     

Elastolysis in lichen ruber planus.

The dermal elastic fiber network was studied in specimens from five patients with lichen ruber planus, using a standard elastin staining procedure (orcein), results being compared with those for the elastin-associated microfibrillar network stained using anti-fibrillin antibodies in an immunofluorescence and an avidin-biotin-peroxidase complex technique. Additional specimens of healed apparently normal skin were taken from two of the patients. Orcein-stained fibers were scarce or absent in the inflammatory zone in all the lesions. In contrast, an extensive fibrillin immunoreactive network was present in the papillary zone in all the specimens, in a pattern similar to that of normal skin. In specimens from healed lesions of lichen ruber planus, dermal orcein-stained fibers were present in the papillary dermis. The findings indicate that the amorphous component of elastic fibers is destroyed during the acute phase of lichen ruber planus. Hypothetically, the elastolysis is caused by elastases released from macrophages known to be present in the lichenoid infiltrate. In contrast, the fibrillin fiber network seems to be less or not at all affected by proteolytic events during the inflammatory phase of lichen ruber planus.