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.     

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.     

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.     

Lichen planus is associated with human herpesvirus type 7 replication and infiltration of plasmacytoid dendritic cells

BACKGROUND: Lichen planus (LP) is a common inflammatory skin disease of unknown aetiology. Viral causes have been suggested. OBJECTIVES: To find candidate viruses associated with LP. METHODS: Lesional and nonlesional skin samples, peripheral blood mononuclear cells and serum were obtained from patients with LP. Ultrastructural, viral DNA, immunohistochemical and serological analyses were performed, and comparisons were made with psoriatic and normal skin. RESULTS: Electron microscopy revealed typical 120-200-nm enveloped particles with a 100-nm nucleus resembling human herpesvirus (HHV) virions both in dermis and in epidermis of lesional LP tissue. HHV-7 DNA was found in 11 of 18 lesional LP samples, as opposed to only one of 11 nonlesional LP samples (P =0.06), two of 11 lesional psoriasis samples (P = 0.05) and none of four normal skin samples. No relation was found between LP skin and DNA of other known HHVs (HHV-1-6 and 8). With immunohistochemistry, significantly more HHV-7+ cells were found in lesional LP epidermis than in normal epidermis. Lesional LP dermis contained significantly more HHV-7+ cells than nonlesional LP, psoriatic or normal dermis. Moreover, LP skin contained overwhelmingly and consistently more plasmacytoid dendritic cells (upregulated in virally induced conditions) than nonlesional LP samples. CONCLUSIONS: We conclude that HHV-7 replicates in LP lesions, but not in psoriasis, another inflammatory skin condition. HHV-7 is possibly involved in the pathogenesis of LP. These preliminary data make further research on this topic of interest.     

The development of manifest psoriatic lesions is linked with the invasion of CD8+ T cells and CD11c+ macrophages into the epidermis

Koebner response was studied in 35 psoriatic patients. Two punch biopsies per patient were taken from non-lesional psoriatic skin before, and 6 h, 2 days, 7 days, 14 days and 21 days after, tape stripping. Alterations in the numbers of CD1+ Langerhans cells, CD4+ and CD8+ T cells and CD11c+ macrophages were mapped morphometrically. Results were compared with lesional and non-lesional psoriatic skin, and control skin. Nine of 35 patients were Koebner-positive. No statistically significant differences were noted between non-lesional psoriatic and control skin. CD4+ T cells increased in number 2 days after trauma in both the epidermis and the dermis, whereas epidermal CD8+ T cells and CD11c+ macrophages increased only in the Koebner-positive lesional skin after 7 days. The changes in lesions induced by tapestripping resembled those seen in lesional psoriatic skin (mature plaques). The number of CD1+ cells increased in mature psoriatic lesions only. It seems possible that trauma per se stimulates the accumulation of CD4+ T cells at the site of injury, but the development of manifest psoriatic lesions correlates with invasion of CD8+ T cells and CD11c+ macrophages into the epidermis.     

Quantitative analysis of contact sites between mast cells and sensory nerves in cutaneous psoriasis and lichen planus based on a histochemical double staining technique

Summary The aim of the present study was to test further our previous hypothesis that the inflammatory reaction in psoriasis is neurogenic. For this purpose, contact sites between mast cells and sensory nerves were morphometrically analysed in the basement membrane zone, papillary dermis and three dermal zones of lesional/non-lesional psoriatic and lichen planus skin as well as in healthy control skin. The analyses were made on sections stained with a histochemical double stain developed for this study. With the double stain, active mast cell tryptase was stained blue enzyme histochemically, and the sensory nerves black using specific monoclonal anti-neurofilament antibodies with immunogold. In psoriatic lesions, both mast cells and mast cell — nerve contacts were markedly more frequent in the basement membrane zone and in the papillary dermis when compared with the corresponding areas in the other groups. Mast cell numbers were increased in both lesional and symptom-free skin in lichen planus, but no increase was found in the mast cell — nerve contacts. Increased contacts between mast cells and sensory nerves indicate that the elements exist for neurogenic inflammation in psoriatic lesions. These increased contacts are not due to the extensive inflammatory reaction only, because they were not observed in lichen planus lesions.     

Mast cell density and IL-8 expression in nonlesional and lesional psoriatic skin

BACKGROUND: An important cellular aberration at sites of psoriatic inflammation is an increase in the number of dermal mast cells. Being multifactorial immune effector cells, it is believed that mast cells play an essential role in perpetuating the inflammatory process of psoriasis. However, factors responsible for the infiltration and accumulation of mast cells in psoriatic lesions are largely unknown. Recent studies have demonstrated that Interleukin-8 (IL-8) exerts strong chemotactic effects on mast cells in vitro. Overexpression of IL-8 has also been reported in psoriatic lesions. In this study, we have found a correlation between the expression of IL-8 and dermal mast cell density in lesional psoriatic skin as compared to nonlesional psoriatic skin. METHODS: Four-mm punch biopsies were taken from 14 psoriatic patients and eight healthy volunteers. Using immunohistochemical techniques, 8 microm sections of lesional psoriatic, nonlesional psoriatic, and normal control samples were evaluated for dermal mast cell density and the density of IL-8 expressing keratinocytes. RESULTS: It was found that dermal mast cell density in lesional psoriatic, nonlesional psoriatic, and normal skin was 105.4 +/- 71.2, 42.3 +/- 30.1, and 47.5 +/- 32.5 mast cells/mm(2), respectively. IL-8+ keratinocyte density in lesional psoriatic, non lesional psoriatic, and normal skin was 171.5 +/- 67.1, 25.4 +/- 14.9 and 20.6 +/- 8.7 IL-8+ Keratinocytes/mm(2), respectively. CONCLUSIONS: The results of this study suggest that increased levels of IL-8 in the keratinocytes of psoriatic plaques play a contributing role in the migration of mast cells to lesion sites.     

Quantitative analysis of tryptase- and chymase-containing mast cells in atopic dermatitis and nummular eczema

The distribution of mast cells (MCs) containing tryptase (T) and chymase (C) was studied in the non-lesional and lesional skin of 26 patients with atopic dertnatitis (AD) and 23 patients with non-atopic nummular eczema (NE). and in the skin of eight healthy controls. T and C activities were demonstrated enzymehistochemically using 2-Gly-Pro-Arg-MNA and Suc-Val-Pro-Phe-MNA as substrates, respectively. The T- and C-containing MCs were counted separately in the epidermis, in contact with the basement membrane. In the papillary dermis and in different dermal levels (0·2 mm each). Also, the C protein was determined immunohistochemically. T-positive MCs were similarly distributed in non-lesional and lesional skin of both AD and NE. The MC number was relatively high in the upper dermis (papillary dermis and levels I and I!) of non-lesional and lesional skin of AD. In the upper dermis of non-lesional AD and NE skin and in normal skin, about 50% of T-positive MCs displayed C activity, whereas the percentage in lesional AD and NE skin was only about 30%. hi this respect, the non-lesional and lesional samples differed significantly froLu each other in both dennatoses (in AD p = 0%005, in NEP = 0·002. Students' t-test). In all samples the MC number decreased in the deeper dermal levels, although numerous T-containing MCs were still counted in the deeper dermis (dermal levels IV-VII) of lesional AD and NE skiti. differing significantly from the MC number in normal skin (In ADp = 0·005. in NE p=0·041). In the deeper dermis. the percentage of MCs containing active C was about 70% in non-lesional and lesional AD and NE. and about 90% in normal healthy skin. However, in the upper dermis of non-lesional and lesional skin of both AD and NE. about H()% of all MCs contained the C protein, which differed significantly from the value of 100% in normal skin (p<0·5). In conclusion, the increased number of T-positive MCs in the upper dermis of non-lesional and lesional AD contributes to promoting inflammation. C apparently loses its activity in the upper dermis of lesional AD and especially in NE. Thus. Ihe enzyme partially lacks its capability to suppress inflammation, such as degradation of neuropeptides and proteins. The dysregulation of these proteinases exists already in non-lesional skin of AD and NE.     

Transient production of stem cell factor in dermal cells but increasing expression of Kit receptor in mast cells during normal wound healing

Mast cells are involved in inflammatory skin disorders and wound healing processes, but the mechanism behind mast cell activation is obscure. In this study, we stained the stem cell factor (SCF) and the Kit receptor in tryptase-positive mast cells, since these molecules are essential for mast cell survival, growth, migration and activation. For this purpose, biopsies were taken from the edge of normally healing wounds of 12 patients undergoing skin transplantation on days 0, 1, 3, 7 and 14, and from chronic leg ulcers and psoriatic skin for comparison. In healing wounds, SCF-positive cells rapidly increased in number in the dermis peaking on day 1, but declined thereafter to their baseline values. The percentage of Kit-positive mast cells increased slowly but steadily reaching a maximum (73+/-22%, P=0.02) on day 14. In chronic ulcers, most of the mast cells were Kit-positive both in the wound bed and in the perilesional skin (87+/-9% and 86+/-13%, respectively). The number of SCF-positive cells was higher in the wound bed than in the dermis of perilesional skin. In the psoriatic skin of ten patients, lesional specimens showed significantly higher numbers of SCF-positive dermal cells as well as a higher percentage (88+/-12% vs 46+/-26%, P=0.004) of Kit-positive mast cells than nonlesional skin. In conclusion, our findings show that the expression of SCF increases rapidly in the early stages of wound healing but declines thereafter, whereas the expression of Kit in mast cells is induced slowly in healing wounds. In chronic wounds as well as in psoriatic lesions, both SCF and Kit are intensely expressed. Thus, it seems possible that SCF and Kit receptor interact, and this could lead to persistent mast cell activation and growth in chronic wounds and psoriasis, whereas only temporary mast cell activation is apparently needed in healing wounds.     

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 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.     

Dermal mast cells in scleroderma: their skin density, tryptase/chymase phenotypes and degranulation

To determine the distribution, tryptase/chymase phenotypes and degranulation of mast cells (MCs) in the dermis of patients with scleroderma, we examined MC density in the skin of 22 patients with systemic sclerosis (SSc) and 11 with localized scleroderma (LSc). We used antitryptase and antichymase antibodies after Carnoy's fixation. Detailed reports of two representative patients with SSc and LSc are included. In the scleroedematous stage (grade 1) showing oedema in both papillary and reticular dermis with variable homogenization of collagen bundles in the reticular dermis, MC skin density was variable in each specimen although MC skin density, as a whole, was significantly increased as compared with normal skin ( P  < 0.05). In the sclerotic stage (grade 2) characterized by homogenization of collagen bundles in the entire dermis, MC skin density was significantly decreased as compared with normal skin ( P  < 0.005). LSc showed changes similar to those in SSc. The ratio of MC_TC cells (both tryptase- and chymase-positive MC) to MC_T cells (tryptase-positive but chymase-negative MC) was variable in SSc and LSc. MC_T cells were exclusively dominant in three patients with SSc and two with LSc. In a patient with SSc (patient 1) showing remarkable perivascular and interstitial oedema in the upper dermis, MC skin density was increased in the oedematous portion and tryptase-positive granules were distributed in extracellular locations. In another patient with LSc (patient 2), tryptase positivity increased and chymase positivity decreased in both number and intensity as the skin sclerosis progressed. MCs must have variable interactions with the lesional skin in SSc and LSc. The present study suggests that MCs are involved in the development of interstitial oedema.     

Decreased chymase activity is associated with increased levels of protease inhibitors in mast cells of psoriatic lesions

Mast cells contain large amounts of the powerful serine proteinases, tryptase and chymase, of which only chymase can be inactivated by serum protease inhibitors. In this study, 20 patients with psoriasis and a control group of 13 with atopic dermatitis were biopsied for lesional and non-lesional skin specimens. The presence of chymase inhibitor alpha 1-proteinase inhibitor (alpha 1-PI), alpha 1-antichymotrypsin (alpha 1-AC), alpha 2-macroglobulin (alpha 2-MG) and C1-esterase inhibitor (C1-Inh) immunoreactivity in mast cells was verified using the sequential double-staining method. Tryptase- and chymase-positive mast cells were stained enzyme-histochemically. Tryptase-positive mast cells were increased in number in the upper dermis of the psoriatic lesion compared with lesion-free psoriatic skin (308 +/- 109 vs. 100 +/- 29 cells/mm2, respectively, mean +/- SD, p < 0.0005, t-test) while the percentage of mast cells showing chymase activity was decreased (76.8 +/- 22.1% vs. 28.6 +/- 14.4%, p < 0.0005). These findings are consistent with our previous ones. In contrast to the decreased percentage of chymase-positive mast cells, a novel finding was that the percentages of alpha 1-AC+ (86.9 +/- 7.2% vs. 59.5 +/- 12.6%, p < 0.0005), alpha 1-PI+ (72.2 +/- 14.9% vs. 33.4 +/- 18.6%, p < 0.0005) and alpha 2-MG+ (16.8 +/- 7.0% vs. 6.2 +/- 3.5%, p < 0.002) mast cells were significantly higher in the psoriatic lesion with the exception of the percentage of C1-Inh+ mast cells (13.7 +/- 10.0% vs. 11.0 +/- 6.1%, p < 0.7). The localization of these inhibitors in mast cells is not a characteristic feature of psoriasis, since mast cells in atopic dermatitis skin also showed immunoreactivity though in slightly lower percentages. Previously, we have shown that MCTC (tryptase+, chymase+) mast cells increase in number in the psoriatic lesion but chymase becomes inactive. The results of this study show again the decreased chymase activity, which could be due to increased levels of its inhibitors (alpha 1-AC, alpha 1-PI and alpha 2-MG) in the same mast cells. Thus, active tryptase could promote inflammation but chymase seems not to be an important mediator in the pathomechanism of psoriasis.     

The development of manifest psoriatic lesions is linked with the appearance of ICAM-1 positivity on keratinocytes

The development of psoriatic lesions was studied in 36 psoriatic patients using the Koebner reaction induced by tape stripping. Two biopsies per patient were taken from non-lesional psoriatic skin before, and 6 h, 2 days, 7 days, 14 days and 21 days after tape stripping. Alterations in HLA-DR, ICAM-1, Ki-67 and FXIIIa positivities in both the dermis and the epidermis were estimated using immunohistochemical methods. A double staining for CD4⁺ and CD8⁺ T cells was also carried out to show their possible Ki-67 positivity. Results were compared with those from lesional (mature plaque) and non-lesional psoriatic skin, and control skin. Of the 36 patients, 9 were Koebner-positive. The most important finding in Koebner-positive psoriatic skin was the appearance of ICAM-1 positivity on epidermal keratinocytes simultaneously with the clinically observed lesion on day 7. The number of FXIIIa⁺ dendrocytes in the dermis was quite constant, and increased in mature psoriatic lesions only. The number of active HLA-DR⁺ immunocompetent cells increased in developing psoriatic lesions, being highest in mature lesions, but no Ki-67 positivity was detected in epidermal or dermal T cells in the psoriatic specimens. Based on these results, it is concluded that T cells divide and are activated extracutaneously in psoriasis, and also that ICAM-1/LFA-1 interactions are important in the recruitment of inflammatory cells and in controlling the effector cell functions.     

银屑病患者皮肤中T细胞与黑素细胞的检测及临床意义

目的 研究银屑病患者皮肤中CD4+和CD8+ T细胞与黑素细胞的关系和临床意义。 方法 取29例进行期银屑病患者皮损和非皮损、5例消退期患者皮损和非皮损及6例健康人皮肤。免疫组化检测CD4+ T细胞和CD8+ T细胞的数量和分布,并对比基底层黑素细胞和色素颗粒情况。采用SPSS18.0软件进行统计分析,多组间比较采用单因素方差分析（ANOVA）,两组间比较采用最小显著差异法（LSD）,相关性分析采用Pearson检验。 结果 银屑病患者皮损中每个高倍（× 200）视野CD4+ T细胞平均数（表皮5.29 ± 4.66,真皮77.50 ± 43.66）明显高于非皮损（表皮为0,真皮9.67 ± 7.73）,皮损与非皮损比较,均P ＜ 0.05;而CD8+ T细胞的数量（表皮7.83 ± 6.27,真皮46.08 ± 34.26）亦明显高于非皮损（表皮0.71 ± 1.20,真皮5.54 ± 4.43）,皮损与非皮损比较,均P ＜ 0.05。与健康对照皮肤相比,银屑病患者皮损中CD4+ T细胞和CD8+ T细胞均明显增多,差异有统计学意义（均P ＜ 0.05）。银屑病皮损处基底层黑素细胞数量（103.45 ± 16.96）明显高于非皮损（43.62 ± 14.20,P ＜ 0.05）及健康人皮肤（P ＜ 0.05）,但色素颗粒阳性细胞比例（7.45% ± 3.86%）明显低于非皮损（43.10% ± 14.91%,P ＜ 0.05）及健康人皮肤（P ＜ 0.05）。非皮损处CD8+ T细胞、CD4+ T细胞、黑素细胞数量及色素颗粒阳性细胞比例与健康人比较差异均无统计学意义。消退期皮损黑素细胞数量高于消退后白斑（P ＜ 0.05）,色素颗粒阳性细胞比例略低于消退后白斑,但差异无统计学意义;与健康人比较,消退期皮损黑素细胞数量高,而色素颗粒阳性细胞比例低,均有统计学差异（均P ＜ 0.05）,消退后白斑的黑素细胞数量与健康人比较差异无统计学意义,而色素颗粒阳性细胞比例降低（P ＜ 0.05）。进行期患者皮损中CD4+、CD8+ T细胞数与黑素细胞数及色素颗粒阳性细胞比例均无相关性（均P > 0.05）,而非皮损中CD4+、CD8+ T细胞数与黑素细胞数呈正相关（r值分别为0.46和0.56,均P ＜ 0.05）,但与色素颗粒阳性细胞比例无明显相关性（P > 0.05）。 结论 在银屑病进行期皮损中,CD4+ T细胞和CD8+ T细胞明显增多,基底层黑素细胞数量增加,但色素颗粒明显减少;皮损消退后,黑素细胞数量及色素颗粒逐渐接近健康人水平。     

Mast cells are one major source of interleukin-4 in atopic dermatitis

Several reports have shown the presence of T-helper lymphocytes with Th2 characteristics in the skin lesions of atopic dermatitis (AD). However. Th2 cells themselves require an exogenous pulse of IL-4 to initiate their differentiation and synthesis of IL-4. As mast cells have recently been shown to contain IL-4, this finding prompted us to investigate IL-4 in mast cells of AD lesions, to determine if they might provide the IL-4 pulse needed by the Th2 cells. In this study, we measured IL-4 immunoreactivity in mast cells of non-lesional and lesional skin sections from 20 patients with AD. Ten patients with nummular eczema (NE) without any atopic features or background, and five healthy subjects, served as the control groups. Mast cells were first identified using an enzyme-histochemical staining method for tryptase. Subsequently, the sections were photographed, the tryptase stain was removed, and IL-4 was demonstrated with a polyclonal antibody. The sections were photographed again, and the percentage of IL-4-positive mast cells was calculated. The percentage of mast cells exhibiting IL-4 immunoreactivity in the upper dermis in lesional vs, non-lesional skin was 66±18% vs. 37±18% in AD (P<0.0001, paired t-test), but only 46±19% vs. 31±22% in NE. In the skin of healthy controls, only 23±25% of the mast cells were positive for IL-4. In addition, a significant difference was found between lesional skin of AD vs. NE patients (P<0.008, unpaired t-test). Moreover, the staining intensity of IL-4 in mast cells was clearly increased in the lesional compared with the non-lesional AD skin. Mast cells appeared to be the main cell type containing IL-4 in 40% of the lesional AD skin specimens, whereas in the remaining 60% prominent IL-4-positive mononuclear cell infiltrates were also present. In the non-lesional skin, mast cells appeared to be the main cell type containing IL-4 in all specimens. These results indicate that mast cells are one major source of IL-4 in lesional and non-lesional AD skin, and they could contribute significantly to the development of AD.