异位性皮炎的记忆性T细胞浸润及ICAM—1表达

为了解粘连分子在异位性皮炎炎症及免疫反应过程中的作用，对ＡＤ皮损部位细胞间粘连分子－１的表达作了研究。结果虽然正常皮肤表皮不表达ＩＣＡＭ－１但ＡＤ皮损处角朊细胞则局灶性表达ＩＣＡＭ－１，尤其在有严重单个核细胞浸润及表皮内淋细胞移入的部位。免疫表型研究表明，ＡＤ真皮浸润中ＣＤ４＾４＋／ＣＤｗ２９＾＋／ＣＤ４５ＲＡ＾－１记忆性Ｔ细胞占主导，推测它们可能通过分泌某些细胞因子而诱导角朊细胞表达ＩＣＡＭ－１     

异位性皮炎皮损中ICAM—1的表达及其临床意义

为了探讨ＩＣＡＭ－１在异位性皮炎（ＡＤ）发病机理中的作用，用免疫组化方法对１６例ＡＤ皮损中ＩＣＡＭ－１的表达进行研究，结果显示，１６例ＡＤ皮损中１４例表皮角朊细胞膜上有ＩＣＡＭ－１的灶性表达，在有表皮海绵水肿处表达强，１６例ＡＤ真皮血管内皮细胞ＩＣＡＭ－１高表达。１０例正常表皮角朊细胞上无ＩＣＡＭ－１的表达。ＡＤ皮损ＩＣＡＭ－１染色评分与临床症状评分有相关性（ｒ＝０．４７６，Ｐ〈０．０５）。提示Ｉ     

红斑狼疮皮损中浸润细胞免疫表型和角质形成细胞HLA-DR抗原表达的研究

应用抗ＨＬＡＤＲ、ＣＤ３、ＣＤ４、ＣＤ８、ＣＤ２０的单克隆抗体和ｓｔｒｅｐｔｒａｖｉｄｉｎｐｅｒｏｘｉｄａｓｅｓｔａｉｎｉｎｇ（ＳＰ）技术对１０名正常人皮肤,１６例ＳＬＥ皮损和１９例ＤＬＥ皮损进行了免疫组化研究。观察到正常人皮肤角质形成细胞未见ＨＬＡＤＲ抗原表达,而ＳＬＥ（６／１６）,ＤＬＥ（８／１９）皮损处角质形成细胞可以表达ＨＬＡＤＲ抗原。在ＳＬＥ、ＤＬＥ真皮内浸润细胞主要为Ｔ淋巴细胞（ＣＤ３＋浸润细胞）,且以ＴＨ细胞（ＣＤ４＋浸润细胞）占优势。另外,还发现在两种ＬＥ表皮角质形成细胞表达ＨＬＡＤＲ抗原处,真皮内可见ＣＤ３＋浸润细胞和激活的Ｔ淋巴细胞（ＨＬＡＤＲ＋浸润细胞）。讨论了ＬＥ皮损角质形成细胞ＨＬＡＤＲ抗原表达及其与病损内浸润细胞免疫表型的关系。ＬＥ皮损处ＨＬＡＤＲ＋角质形成细胞可能具有抗原递呈作用,而角质形成细胞异常表达ＨＬＡＤＲ抗原则可能与真皮内浸润单个核细胞或淋巴细胞释放的ＩＦＮα,ＴＮＦγ等有关。     

钙泊三醇外用治疗可减少银屑病皮损中ICAM—3阳性浸润细胞的 …

目的 了解钙泊三醇局部外用治疗对银屑病皮损中细胞间粘附分子３（ＩＣＡＭ－３）表达的影响。方法 采用ＡＢＣ免疫组化法对２０例银屑病患者皮损与非皮损部位以及皮损部位治疗前后的ＩＣＡＭ－３、Ｋｉ－６７和其它免疫分析的表达进行了研究。结果 银屑病皮损部位ＩＣＡＭ－３阳性浸润细胞的表达均明显高于非皮损部位及正常对照组（Ｐ均〈０．０１），而且ＩＣＡＭ－３的表达和皮损部位Ｋｉ－６７、ＣＤ３等免疫分子的表达呈正相     

1，25－双羟维生素D_3对培养人角朊细胞增殖，细胞形态及HLA－DR，ICAM－1表达的影响

用体外培养人角朊细胞研究了１．２５－双羟维生素Ｄ_３（１，２５（ＯＨ）_２Ｄ_３）对角朊细胞增殖，细胞形态及ＨＬＡ－ＤＲ，ＩＣＡＭ－１分子表达的影响，培养液中加入１，２５（ＯＨ）_２Ｄ_３可使细胞增殖明显抑制。用流式细胞仪测定，１，２５（ＯＨ）_２Ｄ_３处理６天后角朊细胞体积较未处理的明显变大。用免疫组化染色显示１，２５（ＯＨ）_２Ｄ_３对经ＩＦＮ－γ和ＴＮＦａ刺激的角朊细胞ＨＬＡ－ＤＲ和ＩＣＡＭ－１分子表达无明显影响。     

变应性接触性皮炎患者粘附分子及其配体的免疫组化研究

近年，在变应性接触性皮炎（ＡＣＤ）的研究中，人们越来越重视Ｔ淋巴细胞在表皮中的滞留问题，因为Ｔ细胞可借细胞间粘附分子１／白细胞功能相关抗原１（ＩＣＡＭ１／ＬＦＡ１）途径与郎格罕细胞（ＬＣ）及角朊细胞结合，导致抗原递呈，Ｔ细胞活化、增殖及角朊细...     

某些粘附分子在皮肤血管炎中表达的研究

目的 研究某些细胞粘附分子（ＩＣＡＭ－１，ＶＣＡＭ－１，ＥＬＡＭ－１）在皮肤血管炎中的表达及其意义。方法 采用免疫组织化学方法研究皮肤血管炎皮损部和非皮损部细胞粘附分子的表达。结果 皮肤血管炎皮损部粘附分子表达均高于非皮损部及正常皮肤，ＶＣＡＭ－１与ＥＬＡＭ－１表达呈正相关。结论 患者皮损粘附分子（ＩＣＡＭ－１，ＶＣＡＭ－１，ＥＬＡＭ－１０表达上调，提示其参与皮肤血管炎的发病机制。     

1,25—双羟维生素D3对培养人角朊细胞增殖,细胞开矿及HLA—DR…

用体外培养人角朊细胞研究了１－２５－双羟维生素Ｄ３对角朊细胞增殖，细胞形态及ＨＬＡ－ＤＲ，ＩＣＡＭ－１分子表达的影响。培养液中加入１，２５（ＯＨ）２Ｄ３可使细胞增殖明显抑制用流式细胞仪测定，１，２５（ＯＨ）２Ｄ３处理６天后角朊细胞体积较未处理的明显变大。     

用免疫组化法对发疹型药疹皮损中ICAM-1和HLA-DR及LFA-1的检测

目的 探讨细胞间粘附分子－１（ＩＣＡＭ－１）和人类白细胞表面抗原－ＤＲ（ＨＬＡ－ＤＲ）及淋巴细胞功能相关抗原－１（ＬＦＡ－１）在发疹型药疹发病机制中的作用。方法 用免疫组化ＬＳＡＢ法对３４例发疹型药疹患者皮损组织和８例对照皮肤中ＩＣＡＭ－１和ＨＬＡ－ＤＲ及ＬＦＡ－１进行了检测。结果 发现皮损中角质形成细胞表达ＩＣＡＭ－１和ＨＬＡ－ＤＲ,其阳性率明显高于８例正常对照,在真皮的血管内皮细胞也有ＩＣＡＭ－１的表达,真皮浸润淋巴细胞还表达ＬＦＡ－１。结论 ＨＬＡ－ＤＲ、ＩＣＡＭ－１和ＬＦＡ－１参与了发疹型药疹的炎症过程。     

慢性光化性皮炎真皮浸润细胞免疫表型及角朊细胞Fas抗原的表达

目的：研究慢性光化性皮炎（ＣＡＤ）不同时期皮损内浸润细胞免疫表型及Ｆａｓ抗原在角朊名的表达。方法：应用免疫组化技术分别检测了８例患者的早期皮损及９例患者的后期皮损内的真皮浸润细胞免疫表型；同时检测了表皮角朊细胞Ｆａｓ的表达。结果：早期及后期皮损内浸润细胞主要是Ｔ淋巴细胞戌后期皮损内浸润Ｔ细胞的亚群分布不同，早期以Ｔｈ／ｉ细胞为主，而后期则是Ｔｃ／ｓ细胞占多数。早、后期皮损角朊细胞均可表达Ｆａｓ抗原     

ICAM-1 and LFA-1 Expressions in the Lesional Skin of Annular Erythema Associated with Sjögren Syndrome

ICAM-1 and LFA-1 expression was studied in the lesional skin of ten cases of annular erythema associated with Sjögren syndrome. Most of the infiltrating mononuclear cells around blood vessels expressed LFA-1 in addition to its strong expression on vascular endothelial cells and focal expression on the epidermal basal cell layer in 3 cases. ICAM-1 expression on vascular endothelial cells was similar to LFA-1, although relatively focal and weak expression was observed on mononuclear cells. ICAM-1 expression on keratinocytes was focal and limited to the basal cell layer in annular erythema. These findings suggest that strong expression of ICAM-1 on endothelial cells but not keratinocytes and LFA-1 on mononuclear cells might play some role in the induction of skin lesions in annular erythema associated with Sjögren syndrome.     

Investigation of epidermotropism in canine mycosis fungoides: Expression of intercellular adhesion molecule-1 (ICAM-1) and beta-2 integrins

In human mycosis fungoides (MF), interactions between LFA-1 (CD11a/CD18) and ICAM-1 (CD54) are involved in lymphocyte adhesion to keratinocytes. The purpose of this study was to evaluate the expression of ICAM-1, beta-2 integrins and class II major histocompatibility complex molecules (MHC II) on keratinocytes and infiltrating lymphocytes in canine MF. Sections of frozen skin biopsy specimens from normal dogs (n=3) and dogs with MF (n=17) were evaluated by immunohistochemistry for expression of ICAM-1, beta-2 integrins, and class II MHC molecules. Our results demonstrated that in canine MF, ICAM-1 was expressed variably on epidermal and follicular keratinocytes. The extent of keratinocyte ICAM-1 expression did not correlate with the degree of lymphocyte epithelial infiltration, nor with lymphocyte LFA-1 expression. This was especially evident in cases of Pagetoid reticulosis-like disease in which prominent lymphocyte epidermotropism was not accompanied by keratinocyte ICAM-1 expression. Keratinocyte class II MHC molecule expression did not correlate with keratinocyte ICAM-1 expression. In conclusion, in canine MF, the lack of statistically significant correlations between epithelial lymphocyte infiltration and keratinocyte ICAM-1 expression, and between keratinocyte ICAM-1 and lymphocyte LFA-1 staining, suggests that the LFA-1/ICAM-1 pathway is not the major adhesion mechanism between lymphocytes and keratinocytes. It is suspected that different ligands of the LFA-1 integrin (e.g. ICAM-2) or other adhesion molecules (e.g. CD2/LFA-3, VLA-1) might be involved in the epitheliotropism phenomenon in canine MF. These hypotheses cannot be evaluated in the dog at this time owing to the lack of specific monoclonal antibodies.     

Epidermal keratinocytes express the adhesion molecule intercellular adhesion molecule-1 in inflammatory dermatoses

Using indirect immunofluorescence assays on frozen tissue sections of skin from healthy subjects and subjects with inflammatory skin diseases, we found that intercellular adhesion molecule-1 (ICAM-1) was expressed in a cell surface pattern on epidermal keratinocytes at the site of lymphoid infiltration in cutaneous dermatoses. ICAM-1 was not expressed on epidermal keratinocytes in noninflamed skin. Its expression was not related solely to epidermal hyperproliferation, as hyperproliferative, tape-stripped epidermis did not express ICAM-1. We have reported previously that ICAM-1 expression on epidermal keratinocytes was upregulated by treatment with interferon gamma and that activated T lymphocytes bound to cultured epidermal keratinocytes in vitro by lymphocyte function associated-1 (LFA-1) molecules on T cells and ICAM-1 on epidermal keratinocytes. Taken together, these data suggest that upregulation of expression of ICAM-1 is an important feature of cutaneous inflammation.     

Characterization of intercellular adhesion molecule-1 and HLA-DR expression in normal and inflamed skin: modulation by recombinant gamma interferon and tumor necrosis factor

Lymphocytes bind to cultured keratinocytes that are treated with interferon gamma (IFN-gamma) and tumor necrosis factor (TNF). When the lymphocytes are preincubated with antibody to lymphocyte function associated antigen-1 (LFA-1), this adherence is inhibited. Because intercellular adhesion molecule-1 (ICAM-1) is a ligand for LFA-1, we studied the cellular expression of ICAM-1, as well as two other IFN-gamma-inducible antigens, (HLA) human lymphocyte antigens DR and DQ, in both normal and diseased skin. The modulation of these cell surface antigens by IFN-gamma and TNF with the use of short-term organ cultures of skin was compared with isolated keratinocytes grown in a conventional tissue culture system. While in normal skin, keratinocytes did not express HLA-DR, DQ, or ICAM-1, when organ cultures were supplemented with IFN-gamma, rapid induction of keratinocyte ICAM-1 expression occurred after 24 hours; HLA-DR but not DQ expression occurred after 48 hours. TNF also induced keratinocyte ICAM-1 expression (although to a lesser degree than IFN-gamma) but did not induce either keratinocyte HLA-DR or DQ expression. There was good correlation of keratinocyte expression of ICAM-1 and HLA-DR by IFN-gamma and TNF when the epidermis of the organ culture system was compared with the isolated keratinocytes grown in tissue culture. The presence of intraepidermal lymphocytes correlated extremely well with keratinocyte ICAM-1 expression but not with keratinocyte HLA-DR expression in psoriasis, atopic dermatitis, lichen planus, and mycosis fungoides. The intensity of endothelial cell expression of ICAM-1 correlated with the degree of dermal inflammation. We conclude that IFN-gamma, once produced by activated T lymphocytes in the dermis, may be of importance in lymphocyte trafficking in the epidermis by the induction of keratinocyte ICAM-1 expression. The use of the short-term organ culture system, in which there is inducible ICAM-1 expression, provides an experimental bridge between purely in vitro and in vivo investigations to further our understanding of the molecular basis for lymphocyte apposition to keratinocytes in the skin.     

Selective expression of immune-associated surface antigens by keratinocytes in irritant contact dermatitis.

The expression of three immunoregulatory surface antigens by epidermal keratinocytes was studied in irritant contact dermatitis (ICD), in order to assess whether keratinocytes have a modulatory role in the pathogenesis of this disorder. Biopsies were taken from 48-h patch test reactions to six structurally unrelated irritants, and frozen sections immunolabeled with monoclonal antibodies to the major histocompatibility complex class II antigen, HLA-DR, intercellular adhesion molecule-1 (ICAM-1), and the 88-Kd glycoprotein CD36 (OKM5), as well as to the CD3 (T cells) and CD11a (lymphocyte function associated antigen-1, LFA-1) antigens. We found that there was very limited expression of HLA-DR by keratinocytes, with no correlation between the extent of HLA-DR positivity and the degree of T cell infiltration into the epidermis and dermis, suggesting that interferon gamma may not be a significant mediator of ICD at 48 h. In contrast, keratinocytes showed extensive upregulation of ICAM-1, with an excellent spatial association between ICAM-1 expression and LFA-1 positive leucocytes in the epidermis. This indicates that keratinocyte ICAM-1 induction is not restricted to diseases in which antigen presentation is pivotal, but that it has a generalized role in cutaneous inflammatory reactions, promoting the infiltration of leucocytes into the epidermis. Immunolabeling with OKM5 revealed that CD36 is present to a variable degree on keratinocytes in normal skin. Differential changes in the pattern of keratinocyte expression occurred between irritants, in a manner that suggested that the CD36 antigen does not act as an adhesion molecule in ICD, but rather that its expression is related to the proliferative state of the epidermis. The results of this study demonstrate that immune-associated antigens are selectively expressed on the surface of keratinocytes in 48-h ICD biopsies, implying that these cells play an important regulatory role in the development of the inflammatory response to irritant chemicals.     

The effect of methotrexate on the expression of cell adhesion molecules and activation molecule CD69 in psoriasis

BACKGROUND: The mechanism of the action of methotrexate (MTX) in the treatment of psoriasis has not been completely elucidated. OBJECTIVE: To assess the effect of MTX on the expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, activation molecule CD69 and T-cell phenotype in skin specimens from patients with psoriasis. METHODS: We performed an immunohistochemical analysis of the expression of T-cell phenotype and cell adhesion/activation molecules in skin biopsies from patients with psoriasis treated with a fixed dose of MTX (12.5 mg/week). To determine data on the epidermal/dermal T-cell infiltration we carried out a manual quantification. RESULTS: Skin samples prior to therapy showed a moderate to severe inflammatory infiltrate, mainly due to T lymphocytes with a helper/inducer (CD4) phenotype. Most of these cells also expressed ICAM-1 and VCAM-1. Blood vessels showed expression of E-selectin and VCAM-1, and keratinocytes were positive for ICAM-1 staining. The cell infiltrate was reduced after therapy, as well as the expression of cell adhesion molecules. However, we also noted the persistence of the T lymphocyte phenotype CD8(+), expressing the CD69 activation molecule, after the MTX treatment. CONCLUSIONS: MTX downregulates the expression of some adhesion molecules, a phenomenon that may contribute to its anti-inflammatory therapeutic effect in psoriasis. The infiltrating T cells post-treatment have an activated cytotoxic phenotype, which may suggest a pathogenic role in the continuation and/or recurrence of psoriasis.     

Intercellular adhesion molecule expression in the evolving human cutaneous delayed hypersensitivity reaction

Intercellular adhesion molecule-1 (ICAM-1), putatively expressed by antigen-presenting or target skin cells, is a ligand for the lymphocyte function-associated antigen (LFA-1) present on circulating lymphocytes. Immunohistochemistry of normal adult human skin using monoclonal antiserum to ICAM-1 demonstrated focal reactivity restricted to endothelium lining the dermal microvasculature. Delayed hypersensitivity responses elicited with dinitrochlorobenzene in the skin of the same subject were evaluated sequentially over a 96 h period using immunohistochemical and ultrastructural techniques. The first alteration observed consisted of mast cell degranulation within perivenular foci in the superficial dermis at 4 h after antigen challenge. Sparse superficial perivascular T-cell infiltrates were present by 24 h. Progressive staining for ICAM-1 was observed in microvascular endothelium and in dermal dendritic cells between 24 and 48 h. ICAM-1 expression was documented focally within the lower epidermis at 48 h and diffusely within the lower and upper epidermal layers at 96 h. ICAM-1 expression by keratinocytes was consistently associated with T-cell migration into the epidermis, whereas migration was never observed in the absence of ICAM-1 reactivity. Immunoelectron microscopy confirmed ICAM-1 to be exclusively present on endothelial cells, dermal dendritic cells, mononuclear cells, and keratinocytes, and permitted characterization of the patterns of membrane reactivity. ICAM-1 expression by epidermal cells appears to be closely linked to the progressive migration of T cells from the dermis into the epidermis that characterizes cutaneous delayed hypersensitivity.     

Expression of adhesion molecules and their ligands in contact allergy

Abstract Sequential biopsies from skin lesions induced by nickel sulphate and sodium lauryl sulphate, respectively, were investigated with respect to expression of extracellular matrix proteins and adhesion molecules on lymphocytes, endothelial cells, and keratinocytes. The majority of the infiltrating lymphocytes expressed VLA-4, LFA-1, CD44 and ICAM-1, a variable fraction expressed Leu-8 and VLA-5, and few or no cells were positive for VLA-1, VLA-2 and VLA-6. Noteworthy, was that the infiltrating cells showed a substantial amount of fibronectin but relatively small or negliglible presence of laminin, collagen type IV, IgG, IgA. IgM, and albumin. The fibronectin was associated with cell bodies as well as the area surrounding infiltrating cells. The number of infiltrating cells was larger in biopsies from nickel-sulphate induced lesions and the infiltrates contained more fibroneclin than biopsies from lesions induced by sodium lauryl sulphate. However, at the single-cell level, the expression of VLA antigens, LFA-1, CD44 and ICAM-1 was similar in both groups. The endothelial cells of skin biopsies from nickel-sulphate-induced lesions showed a stronger expression of VCAM-1, ELAM-1 and ICAM-I compared to biopsies from sodium lauryl sulphate-induced lesions. In the biopsies from nickel sulphate-induced lesions, the keratinocytes showed a tendency to less VLA-6 expression. These results suggest that fibroneclin plays a role in lymphocyte extravasation or extravascular lymphocyte migration.     

Mast cells of psoriatic and atopic dermatitis skin are positive for TNF-α and their degranulation is associated with expression of ICAM-1 in the epidermis

Abstract The release of cytokines from cutaneous cells may be of major importance in the initiation and development of many inflammatory skin disorders. For example, tumor necrosis factor-alpha (TNF-α), which in healthy skin is found preformed only in mast cells, is able to induce the expression of several adhesion molecules including intercellular adhesion molecule-1 (ICAM-1). Increased expression of ICAM-1 occurs in keratinocytes in lesional skin of psoriasis and atopic dermatitis (AD) and it is considered to be an important initiator of leucocyte/keratinocyte interactions in skin inflammation. We counted the mast cells showing TNF-α immunoreactivity using a double-staining method in nonlesional and lesional skin sections from 12 patients with AD and 12 patients with psoriasis. The percentage of TNF-α⁺ mast cells in lesional and nonlesional AD skin was 36 ± 22% and 21 ± 15% (P < 0.018, paired t-test), respectively, and in psoriatic skin was 16 ± 25% and 15 ± 15%, respectively (P < 0.89, paired t-test). We also cultured whole skin biopsies taken from the healthy-looking skin of psoriatic and AD patients in the presence of mast cell degranulator compound 48/80, which resulted in focal expression of ICAM-1 in the epidermis. In cultured keratinocytes, both histamine and an extract of a human mast-cell line (HMC-1) induced ICAM-1 immunostaining only in occasional cells, but the combination of histamine and the HMC-1 extract resulted in intense ICAM-1 staining in numerous cells. This enhancement of ICAM-1 staining was abolished by preincubation of the HMC-1 extract with anti-TNF-α antibody. These results suggest that the degranulation of mast cells induces the expression of ICAM-1 in keratinocytes probably via TNF-α and histamine. Received: 8 August 1997     

Prurigo pigmentosa: role of ICAM-1 in the localization of the eruption

Immunohistochemical studies were carried out on the skin lesions of two cases of prurigo pigmentosa. There was a predominance of CD4+ cells in the dermal infiltrate, whereas those lymphocytes in the epidermis were mainly CD8+ cells. The majority of dermal and epidermotropic lymphocytes showed an intense expression of lymphocyte function-associated antigen 1 (LFA-1). The number of CD1+ cells was increased in the epidermis. There was intense expression of ICAM-1 by keratinocytes in the erythematous papules. Focal expression of ICAM-1 was still observed in the residual pigmented areas and could explain the recurrence of the lesions at these sites.