Increased nerve growth factor- and tyrosine kinase A-like immunoreactivities in prurigo nodularis skin – an exploration of the cause of neurohyperplasia

Neurotrophins and their receptors play an important role in cutaneous nerve development and reconstruction after injury. Recent developments indicate that this group of molecules not only exert a neurotrophic action, but are also involved in immune responses and inflammation. Prurigo nodularis is a skin disease characterized by neurohyperplasia and intense itch. In the present study, the localization and distribution of nerve growth factor (NGF) and its receptors were explored by immunohistochemical methods, with the aim of detecting the cause of the neurohyperplasia in the disease. In normal healthy volunteers and in uninvolved skin, NGF immunoreactivity was seldom seen in the basal layer of the epidermis or in the dermis. In prurigo nodularis skin, there was also very little NGF immunoreactivity in the epidermis. However, in the dermis, a huge number of cells showed an NGF-like immunoreactivity. In normal skin of healthy volunteers, only a weak staining for tyrosine kinase A (trkA) was seen in the epidermis, whereas in the dermis, there was no trkA staining seen at all. However, in the prurigo nodularis tissue, the hyperplastic nerves clearly showed trkA immunoreactivity, and it seemed that the staining was only present in the axons. By NGF and p75 NGF receptor double-labelling, both immunoreactivities showed weak staining in the epidermis and dermis of normal skin. However, in the dermis of prurigo nodularis, strong staining for both NGF and NGF receptor antibodies was seen. NGF receptor-immunoreactive nerves were more dense in areas where there were more NGF-immunoreactive cells. The results indicate that in prurigo nodularis skin, NGF is overexpressed, locally infiltrated inflammatory cells may be the source of this NGF, and NGF and its receptors may contribute to the neurohyperplasia of the disease.     

Light and electron microscopic immunohistochemical observations of p75 nerve growth factor receptor-immunoreactive dermal nerves in prurigo nodularis

Abstract Prurigo nodularis is an inflammatory skin disease characterized by neurohyperplasia. Neurotrophins and their receptors play a critical role in nerve growth, differentiation, maturation and maintenance, including cutaneous nerve fiber growth and innervation. They may also be responsible for events related to the growth and differentiation control of keratinocytes. To explore the exact distribution of the p75 low-affinity nerve growth factor receptor (p75 NGFr) in the cutaneous nerve components, p75 NGFr immunofluorescence as well as ultrastructural immunohistochemical studies were performed on prurigo nodularis lesional skin and normal human skin samples. The immunofluorescence results revealed that nerve fibers and bundles were increased in number and size in lesional upper dermis with stronger p75 NGFr immunoreactivity than in the corresponding normal tissue. At the ultrastructural level, a lot of nerve fibers clustered together in the prurigo nodularis dermal tissue. The axons were enlarged and branched, but the axons themselves seldom showed any NGFr immunoreactivity. The Schwann cell bodies were extended and irregularly shaped, and tended to separate into many branches enveloping the axons. The Schwann cell membrane showed strong p75 NGFr immunoreactivity. The perineurium cells also revealed strong p75 NGFr immunoreactivity. The Schwann cells inside the perineurium were less p75 NGFr-immunoreactive than those outside the perineurium. The membrane of certain basal keratinocytes showed NGFr immunoreactivity as well. The present results indicate that overexpression of p75 NGFr in Schwann cells and perineurium cells could contribute to the neurohyperplasia in prurigo nodularis. Received: 26 May 1998 / Received after revision: 3 September 1998 / Accepted: 17 September 1998     

Expression of nerve growth factor receptors in cutaneous inflammation

Evidence indicates that the neurotrophin nerve growth factor (NGF) is a mediator of cutaneous inflammatory responses. Cellular responses to NGF are facilitated by two receptors called trk A and p75 neurotrophin receptor (p75^NTR). In the current study we have investigated the expression of these receptors in lesional and non-lesional skin from patients with plaque psoriasis and in normal skin exposed to three times the minimal erythema dose of ultraviolet (UV) B radiation. Trk A immunostaining was confined to the basal keratinocytes in normal skin. There was a significant reduction in trk A immunostaining in both non-lesional and lesional psoriatic skin compared with control skin. In UVB-irradiated normal skin, there was a significant reduction in trk A immunostaining at 4 h after irradiation, which was still evident at 48 h. In normal skin, p75^NTR immunopositive fine nerve fibres were present throughout the dermis and occasionally seen in the epidermis. Thick nerve fibres were evident in the deep dermis and in the middle region of the dermis. p75^NTR immunopositive basal keratinocytes were occasionally seen. There was a statistically significant loss of p75^NTR immunopositive fine nerve fibres in the epidermis of lesional psoriatic skin and a statistically significant loss of p75^NTR immunopositive fine nerve fibres in the dermis in both non-lesional and lesional psoriatic skin. p75^NTR immunopositive thick nerve fibres were reduced in lesional psoriatic skin compared with normal skin. UVB irradiation of normal skin led to a statistically significant decrease in the p75^NTR immunopositive fine nerve fibres in the epidermis at 48 h after irradiation. There was no significant reduction in the dermal p75^NTR immunoreactivity. These results demonstrated that expression of both NGF receptors is decreased following an acute inflammatory stimulus and also in association with a chronic inflammatory dermatosis.     

The occurrence of cutaneous nerve endings and neuropeptides in vitiligo vulgaris: a case-control study

Pioneering studies both in humans and animals have demonstrated an association between the peripheral nervous system and epidermal melanocyte destruction. The presence of certain neuropeptides and neuronal structural markers in peripheral nerve fibres was investigated in involved and uninvolved vitiligo skin and compared with normal healthy skin. A group of 18 vitiligo vulgaris patients and matched healthy volunteers participated in the investigation. The indirect immunofluorescence technique was employed. There was a tendency for a reduction in the number and intensity of low affinity (p75) nerve growth factor receptor immunoreactive (NGFr-IR) basal keratinocytes in involved vitiliginous skin (P<0.06) compared with control skin, while the number of NGFr-IR nerve fibres was significantly increased (P<0.01). The number of calcitonin gene-related peptide (CGRP)-IR nerve fibres in the epidermis and papillary dermis was dramatically increased in involved skin as compared with control skin (P<0.01) and with uninvolved skin (P<0.05). No clear difference could be found in the distribution of vasoactive intestinal polypeptide (VIP)-and neuropeptide tyrosine (NPY)-IR nerve fibres. A different structural appearance of the peripheral nervous system as well as a changed balance of neuropeptides in vitiliginous skin point to a critical role of the nervous system in the pathogenesis of vitiligo. Work was supported by funds from the Medical Faculty of the Karolinska Institute     

Vasoactive intestinal polypeptide in allergic contact dermatitis: an immunohistochemical and radioimmunoassay study

Abstract Vasoactive intestinal polypeptide (VIP) is a neuropeptide with immunomodulatory properties. To elucidate the possible role of VIP in the pathophysiology of cutaneous contact hypersensitivity, we compared involved with uninvolved skin of allergic contact dermatitis (ACD) from nickel-allergic patients. Assays included quantification of VIP-immunoreactive (VIP-IR) nerve fibres and cells bearing immunoreactivity for VIP1 and VIP2 receptors in skin biopsy specimens, and of the concentration of VIP-like immunoreactivity (VIP-LI) in extracts of biopsy specimens. VIP-IR nerve fibres were found in the deeper part of the dermis close to sweat glands and hair follicles. No difference in the presence of VIP-IR nerve fibres was found between involved and uninvolved skin of ACD. VIP1 and VIP2 receptor immunoreactivity was seen on keratinocytes in the basal layer of the epidermis, with no difference between involved and uninvolved skin. Staining was also seen on vessel walls and mononuclear cells in the dermis. The highest staining intensity in the mononuclear cells was noted with the antibodies against the VIP2 receptor. While most of the mononuclear cells were stained in uninvolved skin, a minority of the cells showed a positive signal in involved skin. The concentration of VIP-LI in uninvolved skin was 1.53 ± 0.790 pmol/g and in involved skin 1.41 ± 0.735 pmol/g. It is concluded that there is no significant difference in either the distribution of VIP-IR fibres or the concentration of VIP-LI between involved and uninvolved skin of ACD. However, the number of dermal mononuclear cells showing VIP2 receptor immunoreactivity in skin of ACD was reduced. Received: 4 May 1998 / Received after revision: 12 October 1998 / Accepted: 16 October 1998     

Neuropeptides in the skin of patients with atopic dermatitis

There is increasing evidence that neuropeptides may be involved in the pathogenesis of atopic dermatitis (AD). This study examines whether neuropeptide distribution in the skin of patients with AD differs from normal controls. The distribution and density of several neuro-peptides were examined in lesional and non-lesional skin of AD patients (n= 5) and in normal controls (n= 4) using indirect immunofluorescence and image analysis. Cholinergic innervation was studied using cholinesterase histochemistry. Staining with the general neuronal marker protein gene product 9·5 showed a subepidermal network of nerves with fibres penetrating the epidermis, and nerves around blood vessels, sweat glands and hair follicles. Image analysis of nerves around sweat glands showed a significantly higher nerve density in non-lesional compared with both normal controls and lesional skin (P < 0·05); lesional compared with control skin showed no significant difference. In the epidermis the density of nerves was not significantly greater in non-lesional compared with lesional skin and controls. Calcitonin gene-related peptide immunoreactivity was similar in all subjects except in three of the AD patients, where more nerves appeared to penetrate the epidermis. Substance P immunoreactivity in the papillary dermis was seen in all AD patients hut no controls. Vasoactive intestinal polypeptide and neuropeptide Y staining were similar in all groups. Acetyleholinesterase-positive nerves were found around sweat glands in all subjects, the staining being greatest in non-lesional and least in lesional skin. Occasional nerves were seen in the papillary dermis in lesional skin of two out of the four patients. We have demonstrated quantitative differences in nerve growth in clinically normal skin of AD patients, and altered cutaneous neuropeptide expression in these patients which may contribute to the pathogenesis of AD.     

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.     

Expression of HLA-DR antigen in skin from patients with psoriasis

Using murine monoclonal antibodies against human HLA-DR antigen and against human T cells, we investigated the indirect immunofluorescence staining pattern of involved and uninvolved skin from patients with psoriasis. The staining pattern of involved psoriatic epidermis is different from the pattern seen in uninvolved skin from the same patient and consists of scattered, single HLA-DR positive cells alternating with groups of HLA-DR positive cells. These HLA-DR positive cell clusters can be seen at any level of the epidermis. In some patients, the dermis of involved skin shows prominent accumulations of T cells which are HLA-DR positive and thus represent activated T cells.     

Expression of growth-associated protein 43 and nerve growth factor receptor in human skin: a comparative immunohistochemical investigation.

The growth-associated protein 43 (GAP43) is a neuronal membrane protein involved in axonal growth and regeneration as well as in the modulation of synaptic plasticity. It is present in sensory and sympathetic neurons, where it is consistently associated with the expression of nerve growth factor receptor (NGFr). We investigated, by means of immunohistochemistry, the presence and distribution of the GAP43-immunoreactivity (IR) and of the NGFr-IR in the adult normal human skin from various body regions. In adjacent sections, a comparison with the distribution of the neuronal markers protein gene product 9.5 (PGP 9.5), substance P (SP), and calcitonin gene-related peptide (CGRP) was performed. Our results indicate that in adult human skin 1) a GAP43-IR is morphologically present in epidermal and dermal nerve fibers; 2) a NGFr-IR is associated with neuronal as well as non-neuronal elements of cutaneous nerves; 3) the basal epidermal cell layer expresses a NGFr-IR, which is unevenly distributed according to the different body areas; and 4) there is suggestive evidence for a simultaneous expression of GAP43-, NGFr-, PGP 9.5-, SP-, and CGRP-IR in at least part of the cutaneous nerve fibers. The presence of GAP43-immunoreactive nerve fibers might be a marker of a continuous synaptic remodeling in adult skin, whereas the distribution of the NGFr-IR could be relevant for our understanding of the maintenance of the neuronal-target relationship(s).     

Phenylethanolamine N-methyltransferase-like immunoreactivity in psoriasis. An immunohistochemical study on catecholamine synthesizing enzymes and neuropeptides of the skin

Immunoreactivity for phenylethanolamine N-methyltransferase (PNMT), the enzyme involved in the conversion of norepinephrine to epinephrine, was present in the basal epidermis and upper dermis in 16 patients with psoriasis. The amount of immunoreactivity was increased tenfold in involved compared to uninvolved skin as characterized by computer-assisted image analysis. In skin from healthy volunteers no immunoreactivity could be found. In our subjects, no immunoreactivity was observed for the other catecholamine synthesizing enzymes (tyrosine hydroxylase; dopa-decarboxylase; dopamine-beta-hydroxylase), apart from single tyrosine hydroxylase positive adrenergic vascular nerves. Furthermore, in psoriasis, the immunoreactivity pattern of the peptides somatostatin, substance P, vasoactive intestinal polypeptide and bombesin was in agreement with skin from healthy volunteers.     

神经生长因子受体P75和P140trkAmRNA在寻常型银屑病患者皮损中的表达

目的研究神经生长因子(nerve growth factor,NGF)受体P75和P140trkA在寻常型银屑病发病机制中的作用.方法应用原位杂交技术检测了33例寻常型银屑病患者(18例为进展期,15例为静止期)和10例正常人皮肤组织中两受体(P75和P140trkA)mRNA的表达情况.结果与正常人皮肤比较,寻常型银屑病皮损及非皮损中P75和P140trkA受体mRNA的表达明显上调,且皮损中的表达明显高于非皮损区(P＜0.01);进展期患者皮损与非皮损中P75和P140trkA受体mRNA的表达分别高于静止期患者的皮损与非皮损区(P＜0.01).结论神经生长因子及其两受体可能是参与银屑病病理机制的重要因子.     

Histamine-containing mast cells and their relationship to NGFr-immunoreactive nerves in prurigo nodularis: a reappraisal

The mast cell, which is a histamine-containing cell, has been found to have far more functions in skin inflammation than hitherto understood. To investigate the appearance of mast cells in prurigo nodularis, histamine immunohistochemistry in combination with nerve growth factor receptor (NGFr) double-staining as well as electron microscopic studies were performed. The results revealed that the histamine-containing cell number was increased in the lesional dermis. The mast cell size was also increased and the shape had become more dendritic. They tended to contact the epidermis and even infiltrated into it. In the histamine and NGFr double-staining, both an increased histamine-containing mast cell number and an increased number of NGFr-immuno-reactive nerve fiber profiles were revealed in the upper dermis of the prurigo nodularis lesional skin. Mast cells were seen in close vicinity to NGFr-positive nerves and sometimes even seemingly to contact single nerve fibers. At the ultrastructural level, it is obvious that the mast cell bodies become larger, having more abundant cytoplasm and organelles (e.g. mitochondria), but comparatively fewer characteristic granules. Mast cells were often observed to sprout long dendrites, with or without granules. The cells were also frequently seen to contact other cell types, and a mast cell infiltration into the epidermis was also found. The statistical results of mast cell numbers showed a significant increase in prurigo nodularis lesional skin compared to the normal controls. The present results further indicate that mast cells, together with cutaneous nerve fibers, are actively involved in the pathogenesis of the disease.     

Evidence for gamma-melanocyte stimulating hormone containing nerves and neutrophilic granulocytes in the human skin by indirect immunofluorescence

gamma-melanocyte stimulating hormone (gamma-MSH)-like immunoreactivity has been found by indirect immunofluorescence in nerve fibers and terminals as well as in neutrophilic granulocytes of normal human skin. A preferential localization to sensory nerves was seen; abundant nerve fibers displaying gamma-MSH immunoreactivity were observed as free nerve endings in the basal layer of the epidermis and in the upper dermis, close to the Merkel cells, in Meissner's corpuscles, around the external root sheath of the lower part of the hair follicles, and in nerve bundles of the deeper parts of the dermis. Very few fibers were seen to be associated with sweat glands and most blood vessels, although arterioles were densely innervated. Thus, gamma-MSH should be considered for possible role as a sensory or axon-reflex chemical messenger. Furthermore, the presence of gamma-MSH in neutrophilic granulocytes raises the possibility that gamma-MSH may play a role in the genesis of post-inflammatory hyperpigmentation, nevi, and melanomas.     

Constitutive endothelial and inducible nitric oxide synthase in inflammatory dermatoses

We have used immunohistochemistry to localize the expression of the constitutive endothelial and inducible forms of the enzyme nitric oxide synthase (NOS) in skin from involved and uninvolved sites in patients with atopic dermatitis (AD) and allergic contact dermatitis (CD). Endothelial NOS (eNOS) immunoreactivity was localized to vascular endothelium in the dermis of both involved and uninvolved skin from all patients. Inducible NOS (iNOS) immunoreactivity was found to be closely associated with the upper dermal microvasculature in all the involved AD biopsies, but only in two of 10 uninvolved AD biopsies. CD biopsies were taken from 10 positive skin patch test sites and iNOS immunoreactivity was detected in all of these. iNOS immunoreactivity was detected in only one of the negative patch test biopsies. Both the extent and intensity of iNOS immunoreactivity was lower in CD than in AD skin lesions. The presence of eNOS in the skin is necessary for constitutive NO-mediated dilatation of the dermal vasculature. Induction of iNOS in the dermal endothelium and in perivascular inflammatory cells may be significant with respect to the roles of NO in both the vasodilatory component of the inflammatory response and in the modulation of immune responses in the skin.     

Altered cutaneous innervation in psoriatic skin as revealed by PGP 9.5 immunohistochemistry

Summary There is conflicting evidence in the literature as to whether cutaneous nerves are altered in psoriasis or not. In this study, antibodies to protein gene product (PGP) 9.5 were used to visualize cutaneous nerves in biopsies from involved and uninvolved skin of nine patients with psoriasis and from normal skin of eight healthy controls. A profound reduction in the epidermal nerve fibre density was observed in the involved psoriatic skin. These intraepidermal nerve fibres were also mostly short and found in the basal layer. Only a few nerve fibres were found in the suprabasal layer and they were non-varicose, long fibres going straight up without branching. In the uninvolved skin of psoriatic patients, the distribution and number of the intraepidermal nerve fibres was similar to that observed in normal skin. In the dermis, the distribution and the number of the nerve fibres showed no differences between involved psoriatic skin, uninvolved psoriatic skin, and normal skin. The results support previous studies in which alterations of cutaneous nerves in psoriasis have been described.     

Ultrastructural study of the skin in Sjögren — Larsson syndrome

Summary The ichthyosiform skin and the uninvolved skin of a 5-year-old Japanese female with Sjögren — Larsson syndrome were examined by light and electron microscopy to elucidate the keratinization disorder. Light microscopically, the epidermis of the ichthyosiform skin showed acanthosis, papillomatosis and hyperkeratosis. The horny cells had a basket-weave appearance. The granular cell layer was slightly thickened. Slight round cell infiltration and vascular dilatation were seen in the upper dermis. The uninvolved skin was histologically normal. Electron microscopically, in both ichthyosiform and uninolved skin, abnormal lamellar or membranous inclusions were present in the cytoplasm of horny cells of the epidermis. These inclusions appeared to be derived from some of the lamellar bodies and/or abnormal membranous structures found in the cytoplasm of spinous and granular cells. Mitochondria in the epidermal basal cells were more numerous in the ichthyosiform skin than in the uninvolved skin. These findings indicate that, whether the skin is involved or not, the epidermis of the patient with this disorder may always have a structural abnormality, which may be genetically determined. Local environmental factors may play a role in inducing the acanthosis and papillomatosis of the epidermis.     

Eosinophil cationic protein- and eosinophil-derived neurotoxin/eosinophil protein X-immunoreactive eosinophils in prurigo nodularis

Abstract It is known that eosinophils are actively involved in allergy and inflammation. The granular components of eosinophils, eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin/eosinophil protein X (EDN/EPX), play an important role in such allergic and inflammatory processes. Prurigo nodularis is a chronic inflammatory skin disease with obvious cutaneous nervous involvement. To detect ECP and EDN/ EPX expression in the eosinophils and their relation to nerve fibres in prurigo nodularis, ECP and EDN/EPX single-labelling immunofluorescence, and ECP and PGP 9.5 double-labelling immunofluorescence, were performed. In prurigo nodularis lesional skin, the ECP- and EDN/EPX-containing cells, which were mainly distributed in the upper dermis, were significantly increased in number compared to their numbers in uninvolved and normal skin. The immunoreactivity of ECP and EDN/EPX in prurigo lesional skin was stronger than in uninvolved skin or control skin. The PGP 9.5-immunoreactive nerves were also increased in number in the areas where there were increased eosinophils. The nerves were in close proximity to eosinophils, and occasionally even seemed to be in contact. The present results indicate that the cutaneous nerves and the ECP- and EDN/EPX-containing eosinophils are possibly involved in the pathogenesis of the disease. The close relationship of nerves and eosinophils indicates that the cutaneous nerves may influence eosinophil function in the chronic inflammatory states of prurigo nodularis. ECP and EDN/EPX could thus be released to the local tissue and modulate the inflammation of the prurigo nodularis lesion. Received: 28 August 1999 / Received: 2 January 2000 / Accepted: 20 March 2000     

Enhanced production and secretion of glial cell line-derived neurotrophic factor and nerve growth factor from the skin in atopic dermatitis mouse model

Role of neurotrophic factors including nerve growth factor (NGF) in the mechanism of overgrowth and hypersensitivity of sensory nerve in atopic dermatitis (AD) has been proposed. Glial cell line-derived neurotrophic factor (GDNF) is a member of neurotrophic factors of the nervous systems; however, the role of GDNF in dermatitis is unknown. IL-18 promotes Th2 type allergic condition in skin and various organs in the absence of IL-12. In this report, we evaluated the expression of GDNF in AD and its association with NGF and IL-18. Mice expressing skin-specific IL-18 (KIL18Tg) or caspase-1, an IL-18 converting enzyme, (KCASP1Tg) were used as AD models; GDNF expression was examined by RT-PCR, enzyme immunoassay, and immunohistochemistry. The mRNA expressions of GDNF and NGF were detected in the epidermis and they were increased in the skin of KIL18Tg and KCASP1Tg mice. GDNF protein production in the skin was also elevated in both transgenic mice and mostly expressed at the basal layer of the epidermis as assessed by immunohistochemistry. Furthermore, the number of nerve fibers was increased in KCASP1Tg, suggesting increased cutaneous innervation. The present results suggest that in addition to NGF, elevated production and secretion of GDNF in the skin associated with overproduction of IL-18 may also be a potent causative factor of itching in AD.     

角质形成细胞生长因子及神经细胞生长因子在银屑病患者皮损中的表达

目的 探讨角质形成细胞生长因子(KGF)及神经细胞生长因子(NGF)与银屑病的关系及银屑病皮损中间质细胞与角质形成细胞的相互作用。方法 应用免疫组化技术分别检测33例银屑病患者皮损、8例非皮损和13例正常人皮肤中KGF、KGF受体、NGF、NGF受体的表达。结果 KGF、KGF受体在银屑病患者基底层和棘细胞下层有极强的表达,与非皮损组及正常对照组间差异有显着性(P<0.05),而非皮损组与正常对照组间差异无显着性(P>0.05).KGF、KGF受体在真皮层未见表达。NGF、NGF受体则主要表达在颗粒层和棘细胞上层,皮损组与非皮损组之间及非皮损组与正常组之间均差异有显着性(P<0.05)。结论 银屑病患者皮损中KGF及NGF可能介导了角质形成细胞的增殖与分化不全;银屑病皮损中存在着间质细胞和角质形成细胞相互作用的紊乱。