Studies on fibronectin in the skin

Fibronectin is a glycoprotein mediating contact between cellular elements and collagen. As judged by indirect immunofluorescence studies fibronectin is abundantly present in normal human skin. It is located in the dermo-epidermal junction area, in the papillary and reticular dermis, about epidermal appendages (pilosebaceous units and eccrine sweat glands) and in the vascular and neural structures.     

Studies on fibronectin in the skin

Summary Affected and unaffected skin from patients with vulgar psoriasis and normal skin from a control group were investigated for the presence of fibronectin with an indirect immunofluorescence technique. In the control group, fibronectin is missing in the epidermis, but is found in the basement membrane zone of the dermo-epidermal junction area, in the papillary and the reticular dermis, and in the vascular and neural systems of the skin. The same distribution is also found in unaffected psoriatic skin, whereas in affected skin a change in the distribution of fibronectin is found in the dermis and in the basement membranes, together with the presence of fibronectin in the epidermis, mainly in the cornified layers.     

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

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

Studies on fibronectin in the skin

Fibronectin is an important constituent of normal human skin, mediating cell/cell and cell/fibre interactions. In affected skin in discoid and systemic LE, changes in the distribution of fibronectin in the dermo-epidermal junction and in the papillary dermis are observed with homogenization and degenerative changes, IF negative gaps and slit formation in the dermo-epidermal region, together with IF positive globular bodies and transport of fibronectin into the epidermis. Unaffected skin in LE demonstrates the pattern of fibronectin as found in normal human skin.     

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.     

Elastolysis in lichen ruber planus.

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

Immunohistochemical studies of amyloid P component distribution in normal human skin

The distribution of amyloid P component (AP) in normal human skin was investigated by a light and electron microscopic immunoperoxidase technique, using antibodies to serum amyloid P component (SAP). AP, or an immunologically cross-reactive protein, was found to be specifically localized to the microfibrils of papillary oxytalan fibers and to the peripheral microfibrillar mantle surrounding the elastin core of mature elastic fibers in the reticular dermis; collagen fibers were not stained with anti-SAP. AP was not detected in the dermal-epidermal basement membrane or in the basement membranes surrounding dermal papillary blood vessels and eccrine structures. These findings, which establish the detailed distribution of normal tissue AP in the skin, provide a basis for further studies of the function and behavior of this protein in health and disease.     

Amyloid P components in normal human skin and skin with lesions

Amyloid P component (AP) is a glycoprotein which is found in tissue deposits of all types of amyloid and is identical to and derived from serum amyloid P component (SAP). SAP binds in a calcium-dependent fashion to various ligands, such as agarose, desoxyribonucleic acid, fibronectin, C4-binding protein, glycosaminoglycans and isolated amyloid fibrils. Tissue AP (TAP) is also a constituent of the normal human renal glomerular basement membrane and is, in adult humans, invariably associated with elastic fiber microfibrils in connective tissue throughout the body, including that of blood vessels. In normal human skin anti-AP antibody binding was localized to the microfibrils of oxytalan fibers in the papillary dermis and to the peripheral microfibrillar mantle of elaunin and mature elastic fibers in the reticular dermis. Since SAP binds to fibronectin and glycosaminoglycans, which in turn bind to collagen fibers, TAP on elastic fiber microfibrils may play an important role in the maintenance of the normal dermal architecture and in dermo-epidermal adhesion. Under pathological conditions, AP is found in all forms of cutaneous amyloidosis, including primary localized cutaneous amyloid (PLCA); it is also detectable on keratin bodies, which represent precursor structures for PLCA. The association of AP with elastic fiber microfibrils and amyloid fibrils and their close anatomical relationship in vivo may reflect the significance of AP in the deposition of cutaneous amyloid.     

Fibronectin distribution in nailfold biopsies of scleroderma (systemic sclerosis) patients

The distribution of fibronectin (FN) was studied in skin biopsies of 13 patients with scleroderma (SD), 7 patients with dermatomyositis (D), and 10 normal controls (NC) by direct immunofluorescence. In normal tissues, continuous or segmental linear staining of the dermal-epidermal junction (DEJ) was seen. Papillary, subpapillary dermis, and papillary capillary loops showed a reticular pattern of deposition with fibronectin. Scleroderma patients revealed similar staining in the dermis and DEJ. The reticular distribution of FN appeared to stain more intensely in the dermis than in controls, especially in deeper layers. The amount of FN in walls of blood vessels from SD patients was markedly increased; all dermal vessels stained with FN and revealed considerably thicker walls and larger lumens. FN distribution in DM patients was similar to that seen in SD with an increased amount of FN staining in capillary walls.     

Specificity of dermal mucin in the diagnosis of lupus erythematosus: comparison with other dermatitides and normal skin

Increased dermal mucin is a feature of lupus erythematosus (LE); however, its amount and distribution have not been well characterized. The differentiation of LE from other forms of dermatitis can be challenging when other features of LE are subtle or equivocal. One hundred and thirty‐five skin specimens showing LE, graft vs. host disease, erythema multiforme/fixed drug eruption, lichen planus, polymorphous light eruption (PMLE), urticaria, eczematous dermatitis and psoriasis and normal skin with and without photodamage were collected. The amounts of mucin in the papillary, superficial reticular and deep reticular dermis were scored from 0 to 3 on hematoxylin–eosin (H&E) and alcian blue (AB) stains, and compared between groups. The mean scores in the reticular dermis were significantly higher in LE than in other categories except PMLE and eczematous dermatitis. A combined H&E + AB score of ≥5 in the superficial reticular dermis gave an overall specificity of 85.7% for LE. Mucin in the papillary dermis failed to distinguish among entities. Normal photodamaged skin showed significantly more mucin in the superficial reticular dermis compared to non‐photodamaged skin. While LE is associated with increased mucin deposition, scant to moderate amount of mucin alone has limited specificity and is common in other dermatitides or photodamaged skin.     

Distribution of fibronectin in the skin of patients with scleroderma

The distribution of fibronectin (FN), a major glycoproteic component of extra-cellular matrix, has been studies by an indirect immunofluorescence technique in the skin of 50 normal controls and 19 sclerodermic patients. In the normal skin, FN was present mainly in the papillary dermis, as thin strips and less abundant in reticular dermis, bound to collagen bundles. In scleroderma skins, FN was increased in the deep dermis of extensive and evolutive lesions (11 cases). In an other hand, the distribution of FN was not modified in stabilized lesions (8 cases). We conclude that the detection of FN in the scleroderma skin is an useful marker of the activity of the systemic sclerosis process and we discuss the possible role of FN as a primary matrix for organization of the collagenous connective tissue during the sclerosing process.     

Bullous lichen planus developed on erythema ab igne

Lichen planus developed on erythema ab igne which was induced by repeated exposures to a stove. The clinical and histopathological features of the eruption were an admixture of typical lichen planus and erythema ab igne. Subepidermal bullae were also found on the lichen planus. Direct immunofluorescence tests revealed deposits of fibrin in the basement membrane zone and IgM in the colloid bodies. Indirect immunofluorescence studies detected no circulating antibodies against cutaneous structures in the patient's serum. This study indicates that repeated thermal exposure over a prolonged period may produce lichen planus lesions.     

Basement membrane and connective tissue proteins in early lesions of Kaposi's sarcoma associated with AIDS

Nearly one-third of all young homosexual men diagnosed as having acquired immune-deficiency syndrome (AIDS) develop a disseminated form of dermal Kaposi's sarcoma (KS). Although the histogenesis of KS cells is unclear, certain evidence suggests that the aberrant cells are of endothelial derivation. We have examined the presence and distribution of connective tissue-specific and basement membrane-specific macromolecules by indirect immunofluorescence and immunoperoxidase staining of frozen sections in early cutaneous lesions of KS from individuals with AIDS. The KS cells typically line the spaces between collagen bundles of the reticular dermis. When stained for the connective tissue-specific glycoprotein fibronectin, all Kaposi's sarcoma lesions showed an intense staining pattern, revealing a complex array of linear deposits of antigen that outlined the exterior surface of the collagen bundles. Antibodies to laminin and type IV collagen, both basement membrane-specific macromolecules, produced an intense staining pattern similar to that found with the anti-fibronectin antiserum, indicating that all 3 antigens are closely codistributed. In contrast, antibodies to type I collagen, the major collagen of the dermis, uniformly stained the collagen bundles in the KS lesions and in the normal control skin. Antiserum to factor VIII-associated antigen, an antigen specific to blood vascular endothelium, frequently stained the KS lesions but the staining pattern was diffuse and of variable intensity. The results suggest that KS cells are derived from the endothelium of the blood microvasculature and maintain their secretory phenotype of secreting basement membrane-specific macromolecules.     

Diagnosis of lichen planus pemphigoides in the absence of bullae on normal-appearing skin

A case of lichen planus pemphigoides is described in which bullae and erosions affected the areas of lichen planus only. The diagnosis was confirmed by the finding of linear C3 and IgG deposition in the basement membrane zone (BMZ) of perilesional skin. Indirect immunofluorescence revealed circulating IgG anti-BMZ antibodies and a lamina lucida split was demonstrated by electron microscopy. This case challenges the clinical dogma that the occurrence of bullae on normal-appearing skin is essential for the diagnosis of lichen planus pemphigoides.     

Immunofluorescence abnormalities in lichen planopilaris.

BACKGROUND--Lichen planopilaris is believed to be a variant of lichen planus because both diseases have similar histologic features. However, as the clinical features of the two diseases differ, we conducted immunofluorescence studies to examine the relation between the two conditions more closely. OBSERVATIONS--Direct immunofluorescence was performed on scalp lesions of seven patients with lichen planopilaris. All had abnormal linear deposits of Ig restricted to the basement membrane zone of hair follicles. The deposits consisted of only IgG or IgA in five patients (70%) and of IgG in combination with other Igs in two patients (30%). Basement membrane zone deposits of fibrin were present in only one patient (14%) and were linear in appearance. There was no staining of ovoid bodies. These immunofluorescence abnormalities differ from those associated with lichen planus where basement membrane zone deposits of fibrin are present in almost all patients, where the basement membrane zone deposits are fibrillar in appearance, and where the deposits of Ig over ovoid bodies are common. CONCLUSIONS--The different appearance and composition of abnormal deposits of immunoreactants in lichen planopilaris and lichen planus suggest that the two conditions are different diseases.     

细胞分化标志分子在扁平苔藓皮损中异常表达的研究

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

Coexistence of lichen planus and bullous pemphigoid (an immunofluorescence study of a "lichen pemphigoides") (author's transl)]

A 35 year old black man presented with a generalized eruption of lichen planus; subsequently tense blisters appeared within the lichenoid lesions and on clinically normal skin. Histopathological characteristics of lichen planus were present in the papules, and those of bullous pemphigoid were seen in the bullae taken from non-lichenoid skin. Direct immunofluorescence studies revealed immunological characteristics of lichen planus in skin and mucosal lesions of L. P. Bound IgG and beta1 C/beta1 A with tubular patterns were detected at the dermo-epidermal junction in all the skin fragments (clinically normal skin, bullous lesions lichenoid skin and mucous lesions). Indirect immunofluorescence studies showed at several intervals that the patient had circulating antibasement membrane zone antibodies (IgG; titres 1/50). This is the third published case in which immunofluorescence studies have established the "pemphigoid" nature of some bullous lichen planus. These findings are in favour of an immune disorder in lichen planus.     

Heterogeneous disease: a child case of lichen planus pemphigoides triggered by varicella

Lichen planus pemphigoides (LPP) is a rare and controversial disease. It is characterized clinically by tense bullae arising both on lichen planus papules and on uninvolved skin, histologically by the demonstration of subepidermal bullae and by linear deposits of immunoglobulin G and C3 along the basement membrane zone on immunofluorescence of peribullous skin. Some authors consider LPP as the combination of lichen planus and bullous pemphigoid. Others think that it most likely encompasses a heterogeneous group of subepidermal autoimmune blistering disorders occurring in association with lichen planus. We present a child case that supports the heterogeneous condition of this disease triggered by varicella.     

Immunofluorescence demonstration of type IV collagen and a noncollagenous glycoprotein in thickened vascular basal membranes in protoporphyria.

Specific rabbit antibodies to type IV collagen isolated from a basement membrane producing mouse tumor were used in indirect immunofluorescence tests to study the thickened vascular basement membrane in skin biopsies from patients with erythropoietic porphyria (EPP) and from protoporphyric mice. In addition, rabbit antibodies to a noncollagenous, basement membrane specific glycoprotein also derived from the mouse tumor were tested. It was shown that normal as well as altered vascular basement membranes in both the human and the murine skin specimens react with the anti-type IV collagen and the antiglycoprotein antibodies. A particular strong reaction in the diseases skin indicated that formation of new vascular basement membrane layers involved deposition of the major structural proteins which also constitute normal basement membrane matrices.     

Alterations in distribution of tenascin, fibronectin and fibrinogen in vulval lichen sclerosus

BACKGROUND: The pathophysiology of lichen sclerosus remains uncertain. The clinical features, including increased fragility and scarring, and the histology suggest that significant reorganisation of the extracellular matrix is occurring. Tenascin, fibrinogen and fibronectin are extracellular matrix components that play a significant role in tissue remodelling, for example during wound repair. Aim: To examine the distribution of tenascin, fibrinogen and fibronectin in vulval lichen sclerosus. MATERIALS AND METHODS: Immunohistochemical staining was performed to study the distribution of tenascin, fibronectin and fibrinogen in 16 specimens of untreated vulval lichen sclerosus and 1 specimen of extragenital lichen sclerosus. Haematoxylin and eosin staining of the specimens was also performed to identify the position of the pale staining homogenous zone/zone of sclerosis and the inflammatory infiltrate below this. The control tissues studied included biopsies taken from the uninvolved thigh of 13 of the lichen sclerosus patients and 6 samples of normal vulva tissue obtained during gynaecological procedures from women of similar age to the lichen sclerosus women. RESULTS: All the lichen sclerosus specimens demonstrated increased immunostaining of tenascin in the upper dermis and comparing this with the haematoxylin and eosin staining this corresponded to the zone of sclerosis with relatively little tenascin staining associated with the inflammatory band. In 14 out of the 16 vulval lichen sclerosus specimens and the extragenital lichen sclerosus specimen fibrinogen immunostaining was increased in the upper dermis which corresponded--in haematoxylin and eosin staining --to the zone of sclerosis. There was also slightly increased fibrinogen staining in the mid dermis which corresponded to the inflammatory band. Fibronectin staining was reduced in the upper dermis of 12 of the vulval lichen sclerosus specimens and the extragenital lichen sclerosus specimen which corresponded to the zone of sclerosis. However, in 14 of the vulval lichen sclerosus specimens and the extragenital lichen sclerosus specimen, fibronectin was slightly increased in the mid and deeper dermis which corresponded to the zone of inflammatory cells and the area below this. There was also increased fibronectin staining around blood vessel walls both in the mid dermis and within the zone of sclerosis. CONCLUSION: The distribution of tenascin, fibrinogen and fibronectin is altered in lichen sclerosus and the alteration in these extracellular matrix components may be relevant to the initiation of scarring in lichen sclerosus and the associated increased skin fragility.