免疫-神经-皮肤网络与紫外线

皮肤中的神经纤维可以分泌多种神经调质如降钙素基因相关肽、P物质、神经肽Y等。皮肤中的角质形成细胞、黑素细胞、成纤维细胞都有表达阿黑皮素原及其衍生肽包括促肾上腺皮质激素、α -促黑素等神经肽的潜力。神经肽还可来自于免疫细胞 ,如朗格汉斯细胞、淋巴细胞、巨噬细胞等。他们之间形成一个复杂的免疫神经皮肤网络。紫外线照射皮肤可以调节这个网络合成和分泌神经调质 ,导致黑素合成和免疫抑制反应的发生 ,在皮肤的生理和病理过程中发挥重要作用     

免疫-神经-皮肤网络与紫外线

皮肤中的神经纤维可以分泌多种神经调质如降钙素基因相关肽、P物质、神经肽Y等。皮肤中的角质形成细胞、黑素细胞、成纤维细胞都有表达阿黑皮素原及其衍生肽包括促肾上腺皮质激素、α-促黑素等神经肽的潜力。神经肽还可来自于免疫细胞，如朗格汉斯细胞、淋巴细胞、巨噬细胞等：他们之间形成一个复杂的免疫神经皮肤网络。紫外线照射皮肤可以调节这个网络合成和分泌神经调质，导致黑素合成和免疫抑制反应的发生，在皮肤的生理和病理过程中发挥重要作用。     

内皮素和降钙素基因相关肽与变应性皮肤血管炎相关性研究

变应性皮肤血管炎（allergic cutaneous vasculitis，ACV）是一种主要累及真皮浅层小血管和毛细血管的过敏性、炎症性皮肤病。内皮素（endothelins，Err）和降钙素基因相关肽（calcitonin gene related peptide，CGRP）是两种相互拮抗的具有多种生物学效应的神经肽，在机体内分布广泛，对各系统特别是心血管系统具有重要调节作用。笔者采用放射免疫法测定37例ACV患者血浆中ET和CGRP水平，旨在探讨ET和CGRP在ACV发病中的作用及其临床意义。     

白癜风患者血浆三种神经肽测定及其临床意义

目的：β内啡肽（β－EP）、神经肽Y（NPY）及降钙素基因相关肽（CGRP）是重要的神经递质,同时也可作为免疫调节因子发挥作用。本研究旨在观察这些神经肽是否可能与白癜风的发病有关。方法：用放射免疫分析法测定40例白癜风处于进展期或稳定期的不同类型患者血浆3种神经肽浓度,并与23例正常对照作比较。结果：寻常型（局限性与泛发性）、节段型、进展期和稳定期白癜风患者血浆β－EP、NPY水平均较正常对照组显著增高;进展期白癜风NPY比稳定期显著提高;泛发性及进展期白癜风血浆CGRP比正常对照组显著增高。结论：结果表明上述三种神经肽与白癜风的发病可能存在一定关系,开发神经肽拮抗剂对于白癜风的治疗可能成为一种新的途径。     

白癜风皮损中NPY VIP和SP的研究

目的 探讨NPY（神经肽Y）、VIP（血管活性肠肽）、SP（神经肽P物质）在白癜风发病机制中的作用。方法 采用SABC免疫组化法对20例白癜风患者（活动期10例，稳定期10例）的皮损、非皮损区以及10例正常人皮肤中的NPY、VIP和SP进行研究，并测定各组皮肤标本中NPY、VIP及SP的免疫反应性。结果 活动期白癜风皮损中NPY、VIP及SP的免疫反应性明显增强，与正常对照及未受累皮肤比较差异有差异性，NPY与SP的反应在白癜风活动期皮损与稳定期皮损比较差异也有显著性。VIP的免疫反应性在白癜风活动期皮损与稳定期皮损中相比稍增强，但差异无统计学意义。结论 神经多肽与白癜风的发病有关，尤其与白癜风的活动性有关。NPY和SP可能在白癜风的发病机制中也起一定的作用。     

胃泌素释放肽及其受体在瘢痕疙瘩中的表达和临床意义

目的研究瘢痕疙瘩内胃泌素释放肽(GRP)及其受体(GRPR)的表达,探讨其在瘢痕疙瘩中的作用。方法使用蛋白质印迹分析检测瘢痕疙瘩及正常皮肤组织内的GRP含量,实时定量PCR检测瘢痕疙瘩及正常成纤维细胞上的GRPR表达。结果瘢痕疙瘩的GRP及GRPR表达均较正常表达升高,差异有统计学意义(P<0.05)。结论瘢痕疙瘩的GRP及GRPR过表达可能在瘢痕疙瘩的发生发展过程中有重要作用。     

蕈样肉芽肿合并白癜风2例报告

目的：探讨蕈样肉芽肿（MF）合并白癜风的机制。方法：对2例MF色素脱失处和色素正常处皮肤活检，进行HE和Fontans染色，检查黑素细胞的分布情况。结果：2例患者的皮肤色素脱失处基底层均未见黑素颗粒，符合白癜风的病理改变；色素正常处皮肤的表皮基底层有较多黑素颗粒存在，真皮上部有黑素颗粒滴落和散在噬黑素细胞。2例患者色素脱失与色素正常处真皮内淋巴细胞浸润和分布情况不一致。结论：MF患者皮肤黑素细胞的缺失可能与其被淋巴细胞的破坏有关，而物理治疗可能促进了这种变化。     

神经肽在紫外线辐射诱导皮肤光损伤性疾病中的作用

神经肽是一类小分子肽,属于细胞外信使家族,作为维系皮肤与神经-免疫-内分泌网络系统的重要信号分子,神经肽在维持皮肤内环境稳态和多种病理生理过程中起到重要的作用。近年来研究发现,当皮肤受到紫外线辐射后,中枢神经细胞、外周感觉神经纤维和皮肤细胞可分泌多种神经肽,参与调控细胞凋亡、炎症反应、黑素生成、免疫抑制、细胞外基质降解等多种急慢性皮肤光损伤发病过程。本文综述常见神经肽在皮肤光损伤性疾病中的主要作用,以期为其防治提供新的思路和分子靶点。     

慢性湿疹皮损处P物质、血管活性肠肽的检测

目的检测P物质(Substance P,SP)、血管活性肠肽(Vasoactive Intestinal Polypeptide,VIP)在慢性湿疹皮损处的表达,探讨神经肽对慢性湿疹患者发病的影响。方法以60例慢性湿疹病人皮损为试验组,20例健康皮肤为对照组。组织病理采用石蜡切片HE染色观察;免疫组化采用SP法。实验结果采用SPSS10.0统计软件中单因素方差分析及等级资料的秩和检验。结果60例慢性湿疹皮损中42例P物质有表达,主要表达于表皮全层、真皮内,范围 ～ ,20例对照组皮肤仅6例有表达,主要表达于表皮基底细胞层,范围 (P<0.05)。60例慢性湿疹皮损中均有VIP的表达,均为胞浆着色,染色位于在表皮及真皮、真皮乳头、血管、毛囊、汗腺周围,色棕黄,范围 ～ 。对照组中也均有表达,但局限于表皮,真皮很少有表达,且颜色为浅黄色,范围 (P<0.05)。结论本研究结果表明,慢性湿疹皮损SP、VIP表达增加;两组比较差异有显著性(P<0.05)。SP、VIP与湿疹的发生发展有一定相关性。     

皮肤神经肽

神经肽在神经冲动的传导下作为介质,并在神经系统和其他细胞群间作为信使起作用。皮肤中含有多种神经肽,它们参与炎症、瘙痒、体温调节、免疫调节。皮肤营养和有丝分裂原作用亦受神经肽影响。本文综述了皮肤中的一些主要神经肽的机能。     

A non-invasive tape absorption method for recovery of inflammatory mediators to differentiate normal from compromised scalp conditions

Background/aims: A simple non-invasive tape (Sebutape^TM) adsorption method was used to recover inflammatory proteins from normal and compromised human scalp (i.e. dandruff and seborrheic dermatitis) in order to assess the inflammatory and immunologic changes relevant to these clinical conditions. Methods: The scalps of subjects identified by a dermatologist as having either dandruff (n = 18), seborrheic dermatitis (n = 19) or normal scalp (n = 16) were visually graded to obtain total adherent scalp flaking scores (TASFS). Sebutape samples were then collected from both the high and low TASFS scalp sites using a one-minute tape application. To recover inflammatory molecules, tapes were extracted in buffered saline with sonication and the tape extracts analysed using commercial immunoassay methods for pro-inflammatory cytokines [i.e. interleukin-1α (IL-1α), IL-1β, IL-1 receptor antagonist (IL-1ra), IL-8 and tumor necrosis factor-α (TNF-α)] and the immunologic cytokines [i.e. IL-2, IL-4, IL-10, IL-12, IL-15 and interferon gamma (IFN-γ)]. Nitric oxide (NO) was also assayed on tape extracts using the Greiss reaction. To account for differences in protein loading on the tapes all cytokine and NO results were normalized using the total protein (TP) amounts recovered in tape extracts. Results: The IL-1α/TP levels recovered from dandruff and seborrheic scalps were significantly decreased (P = 0.03) compared to normal appearing scalp levels. The scalp levels of IL-1ra/TP and the ratio of IL-ra to IL-1α were significantly (P = 0.002) or directionally (P = 0.07) higher in seborrheic dermatitis scalps and dandruff scalps, respectively, compared to normal scalps. The IL-1ra and the IL-1ra/IL-1α ratio values correlated well with the TASFS. The TNF-α/TP levels recovered from dandruff scalps were significantly higher (P = 0.02) than levels recovered from seborrheic dermatitis and normal scalp subjects. IL-2/TP was significantly increased (P = 0.01) and IFN-γ and NO significantly decreased (P = 0.05) in the seborrheic dermatitis scalp samples compared to normal controls. Conclusion: The Sebutape method has proven useful for distinguishing normal from diseased scalp conditions. The cytokines recovered from the scalp tape samples showed distinct patterns that differentiated dandruff, seborrheic dermatitis and normal scalp populations. These methods may also prove useful for monitoring the clinical efficacy of therapeutic actives for treating dandruff and seborrhea.     

Hair counts from scalp biopsy specimens in Asians.

BACKGROUND: Differences in hair density have been described according to the ethnic background in whites and blacks. Asians are known to have fewer hairs than whites. OBJECTIVE: We performed this study to assess the normal values of hair counts in scalp biopsy specimens from Koreans. METHODS: A total of 35 subjects with clinically normal occipital scalps (13 patients with androgenetic alopecia, 20 with patchy alopecia areata, and 2 healthy volunteers) were included. Horizontal sections of 4-mm punch biopsy specimens from clinically normal occipital scalps were examined at various levels from the papillary dermis to the subcutis, and follicular counts of terminal/vellus hairs and anagen/telogen hairs were obtained. RESULTS: The numbers of total hairs, terminal and vellus hairs, and terminal anagen hairs were significantly lower (P <.05) in Koreans compared with the published data of whites and blacks. Percent ratio of terminal anagen and telogen hairs were similar to whites and blacks. Follicular density was significantly lower (P <.05) in Koreans than in whites and blacks. In Koreans, female subjects had a significantly higher number of terminal hairs than male subjects (P <.05). CONCLUSION: Hair density is significantly lower in Koreans than in whites or blacks. Slight sexual difference exists in follicular counts in Koreans. Our data could be used as a guideline for determining normalcy in interpreting horizontal sections of scalp biopsy specimens from Asians.     

Neuropeptides concentrations in the skin of a murine (NC/Nga mice) model of atopic dermatitis

BACKGROUND: It has been reported that the expression of neuropeptides (NPs), and the density and structure of peripheral nerves in atopic dermatitis (AD) are different from those in normal skin. OBJECTIVE: We investigated the role of NPs, in the development of AD with quantitative study of substance P (SP) and calcitonin gene-related peptide (CGRP) in the skin of AD-model mice. METHODS: We measured the NPs in the skin of mice (NC/Nga as AD-model mice, BALB/c and C57BL/6 as control) by enzyme-linked immunosorbentassay (ELISA). Peripheral nerve fibers and SP in the skin were stained by immunohistochemical staining, using anti-PGP9.5 antibody and anti-SP antibody. RESULTS: Under conventional condition, SP concentration in AD-like skin lesions of NC/Nga mice was higher than that in non-affected skin of the same mice. Under specific pathogen-free condition, SP concentration in the skin of NC/Nga mice was higher than that in the skin of BALB/c and C57BL/6 mice. In contrast, CGRP concentration in the skin lesions was lower than that in non-affected skin of NC/Nga mice. SP was detected not only in the nerve fibers in the dermis but also in mast cells in the inflammatory areas. CONCLUSIONS: The skin of NC/Nga mice contains more SP congenitally, and environmental factors may aggravate this abnormal condition. We hypothesize that increase of SP accompanied with a decrease of CGRP in the skin may play important roles in the pathogenesis and development of AD.     

Expression of interleukin 1 in burn scars.

A histochemical study using a Biotin-Streptavidin procedure for demonstrating interleukin 1 (IL-1) in burn scar specimens is described. Among seventeen scar specimens, five positive reactions to IL-1 were observed in the epidermis. No positive reactions in the dermal tissue, however, were detected. The twenty specimens of normal skin used as controls showed no positive reaction in either the dermis or the dermis.     

Immunohistologic and ultrastructural comparison of the dermal papilla and hair follicle bulb from "active" and "normal" areas of alopecia areata.

The "active" edges of patches of alopecia areata and normal areas from the same scalp (i.e., bearing normal terminal hair) from seven patients with alopecia areata were investigated immunohistologically. Similar areas from a further eight patients were examined using light and electronmicroscopy. "Active" and "normal" areas of alopecia areata scalps were immunohistologically similar and varied from normal controls in the number, distribution, and ratio for T4 and T8-positive cells. Similarly the ultrastructural changes seen in the "active" areas when compared to normal controls were also present in the "normal" areas of alopecia areata scalps. The most significant differences found between normal "control" follicles and both "active" and "normal" areas of alopecia areata scalps were the polymorphic nature of the dermal papilla cells and the loss of cellular organization within the dermal papillae taken from alopecia areata scalps. In addition, the junction between the dermal papilla and the bulb of the hair follicle, the dermo-epithelial junction of the hair follicle bulb, demonstrated critical changes in follicles taken from both "active" and "normal" areas of alopecia areata scalps. These results support the suggestion of a subclinical state of alopecia areata and indicate that further work on the etiology of alopecia areata should be directed towards the "normal" areas of alopecia areata scalps, in particular the cells of the dermal papilla and the dermo-epithelial junction of the hair follicle bulb.     

Expression of the L-fucose moiety on infrainfundibular follicular keratinocytes of terminal follicles, its decreased expression on vellus and indeterminate follicles of androgenetic alopecia, and re-expression in drug-induced hair regrowth.

The distribution of various glycoprotein molecules on the surface of follicular keratinocytes was studied with a panel of lectins with specificity for various sugar moieties on biopsy specimens from both bald/balding scalp and normal occipital scalp, of 23 patients with androgenetic alopecia as well as on biopsies of normal forearm skin of four patients. The most significant differences between bald and normal scalp biopsy were noted with Ulex europaeus agglutinin I (UEA I). We noted an increased (91.8% +/- 3.1; mean +/- SE) expression of UEA I binding sites on the infra-infundibular follicular keratinocytes in anagen terminal scalp hairs, compared to 28.5% +/- 5.2 in the indeterminate (anagen) hairs of balding scalps, and 23.2% +/- 6.3 in the anagen follicles of vellus fore-arm hairs. By contrast, the telogen hairs demonstrated minimal UEA I staining: 4.0% +/- 0.8, mean +/- SE in telogen scalp hairs, 1.8% +/- 0.5 in telogen hairs of balding scalps (0% in completely bald scalps, in which all the hairs were in the telogen phase), and 1.9% +/- 0.2 in telogen forearm hairs. The percentage of UEA I staining correlated with the length of the infra-infundibular follicles in all cases studied. In three cases of hair regrowth after hair growth promotors, the UEA I staining increased to 80.6% +/- 6.1 in anagen hairs and correlated with increased length of infra-infundibular follicles. Our data indicate that there are 1) marked differences between anagen and telogen follicles in UEA I binding to infra-infundibular follicular keratinocytes; 2) the percentage of UEA I staining reflects the size (length) of the infra-infundibular hair follicle; and 3) the anagen follicles of balding scalps (indeterminate hairs) show UEA I staining resembling that exhibited by anagen follicles of vellus hairs.     

Hair counts in scalp biopsy of males and females with androgenetic alopecia compared with normal subjects

Background:  Hair counts were studied in scalp biopsy specimens of androgenetic alopecia (AGA) in male and female patients. We also assessed the normal value of hair count in scalp biopsy specimen from Iranians and compared with published data.
Methods:  Thirty subjects with clinically normal scalps, 25 male and 28 female patients with AGA were studied. Vertical and horizontal sections of 4-mm punch biopsy specimens were examined at various levels from the papillary dermis to the subcutis. Hair counts of total, terminal, vellus, anagen and telogen hairs were obtained by ocular micrometer.
Results:  Hair counts were not significantly different from published data in American Whites but significantly higher in Iranians compared with Koreans (p < 0.001). There was no significant difference between male and female patients with AGA. Perifollicular inflammation was lower in both the normal subjects and the patients compared with other studies.
Conclusion:  In AGA patients, total and vellus hairs were lower and terminal to vellus (T:V) ratio was higher than the results of previous studies in Whites (p < 00.1). T:V ratio of control group was significantly higher in this study compared with previous published data. Perhaps the higher ratio than the reported data could means the onset of miniaturization.     

Cytokeratin 15 expression in central, centrifugal, cicatricial alopecia: new observations in normal and diseased hair follicles

Background: Cytokeratin 15 (CK15) is a useful marker for the bulge zone (BZ) and has been used to examine follicles in cicatricial alopecia. We studied the expression of CK15 in hair follicles of patients with central, centrifugal, cicatricial alopecia (CCCA) in an attempt to define BZ integrity. Methods: A commercially available antibody to CK15 was used on formalin‐fixed, paraffin‐embedded tissue from clinically and histologically ‘normal’ scalps, clinically diseased scalps from patients with CCCA and clinically ‘normal’ scalps from patients with CCCA. Results: In both normal and diseased follicles, CK15 expression was closely linked to anatomical zone cellular morphology. Normal and abnormal inner root sheath (IRS) desquamation occurred in concert with predictable cellular morphological changes and CK15 expression. In most abnormal follicles, once the IRS desquamated, the morphology of BZ epithelium changed and CK15 expression disappeared. Conclusions: CK15 highlights BZ cells in normal human follicles, but may be unreliable for this purpose in diseased follicles. CK15 should not be the sole marker for studying stem cells in cicatricial alopecia because any disease‐induced structural changes could alter CK15 expression. More sophisticated studies of stem cells will be required to reliably define their role in the pathogenesis of cicatricial alopecia. Sperling LC, Hussey S, Wang J, Darling T. Cytokeratin 15 expression in central, centrifugal, cicatricial alopecia: new observations in normal and diseased hair follicles.     

Immunofluorescent studies of complement C3 in the hair follicles of normal scalp and of scalp affected by alopecia areata

The deposition of complement C3 in the hair follicles of scalps of 4 normal subjects and of the affected parts of 9 patients with alopecia areata was found by the direct immunofluorescent methods. No deposition of immunoglobulins (IgG, IgA, IgM, IgD and IgE) was found. In the normal scalps, complement C3 was found to be deposited in the hyaline membrane of the hair bulb and in the internal layer of connective tissue sheath at the lower about 2/3 transient portion of anagen follicles, and in the thickened hyaline membrane of the catagen follicles. The deposition of complement C3 was also found in the anagen and catagen-like hair follicles even in the patients with alopecia areata, which was similar to the finding in the normal scalps. From the fact that the deposition of complement C3 was found chiefly in the transient portion of the hair follicles of the normal scalps, and that the behavior of deposition of complement C3 reflected the morphological state of hair follicles in each stage of the hair cycle, even in alopecia areata, complement C3 may be intimately related to the hair cycle, even though its significance is as yet unknown.     

CD103+T细胞在银屑病皮损中的表达

目的：明确银屑病患者皮肤CD103+T细胞的表达及其与银屑病严重程度的关系。方法：免疫组化检测29例银屑病患者皮损和非皮损皮肤及6名健康对照皮肤中表皮及真皮CD103+T细胞的表达。计算银屑病患者PASI值。结果：CD103+T细胞主要在真皮表达。银屑病患者皮损和非皮损真皮中每个高倍视野CD103+T细胞百分率分别为（26.06%±11.72）%和（12.82±4.5）%（P<0.05）;健康人对照皮肤真皮内CD103+T细胞百分率为（7.47±1.3）%,明显低于银屑病非皮损区（P<0.05）。银屑病患者皮损中,CD103+T的表达与PASI值正相关（P<0.05）。 结论：真皮中CD103+T细胞可能与银屑病的发病及严重程度有关。