Lysozyme in abnormal dermal elastic fibers of cutaneous aging, solar elastosis and pseudoxanthoma elasticum

Staining of elastic fibres with antilysozyme antibodies has been noted previously. In this study, we examined the staining pattern of dermal elastic fibres in aging, solar elastosis, and lesional skin of pseudoxanthoma elasticum (PXE) using an antibody to lysozyme and the indirect-peroxidase technique. To assess the effects of aging, sun-protected skin (buttock) from a younger and an older group of patients was used. Sun damage was studied in skin specimens from varying sun-exposed body regions (trunk; head and neck). No staining was seen in sun-protected skin from younger individuals, whereas sun-protected skin from older persons had scattered positive fibres. Solar elastotic material was intensely positive and the number of positive fibres appeared to correlate with the amount of sun damage. Abnormal elastic fibres in PXE also stained positively, but less intensely, than fibres in solar elastosis. This study shows that changes in the elastic fibres due to degenerative processes or genetic factors results in altered antigenic expression of the fibres. This may be an epiphenomenon secondary to changes in proteoglycans, which are known to occur with solar elastosis and PXE, or may represent an adaptive phenomenon to maintain the elastic properties of the altered fibres or to decrease their antigenicity.     

Increased deposition of fibulin-2 in solar elastosis and its colocalization with elastic fibres

BACKGROUND: Fibulin-2 is a 195-kDa protein belonging to a novel family of extracellular matrix proteins that might be involved in microfibril and elastic fibre organization. OBJECTIVES: To determine the localization of fibulin-2 in relation to elastic fibres in normal skin and in solar elastosis characterized by increased elastotic material in the papillary dermis. METHODS: The expression and synthesis of fibulin-2 was investigated by means of in situ hybridization, immunohistochemistry and Western blot analysis in normal and photoaged skin. RESULTS: Immunohistochemistry and elastic tissue staining revealed that fibulin-2 deposition mainly colocalized with microfibrils and elastin fibres, with a marked staining of elastotic material in solar elastosis. Western blot analysis demonstrated that in photoaged skin fibulin-2 showed the same electrophoretic mobility as in sun-protected skin. However, in actinic elastosis the amount of fibulin-2 was significantly higher. In addition, smaller degradation products were detectable, presumably reflecting increased proteinase activity in photodamaged skin. CONCLUSIONS: This study shows that deposition of fibulin-2 and elastin is highly co-ordinated, indicating that this protein plays an important role in elastic fibre and microfibril formation in normal and actinically damaged skin.     

Acquired disorders of elastic tissue: part I. Increased elastic tissue and solar elastotic syndromes

Elastic fibers in the extracellular matrix are an integral component of dermal connective tissue. The resilience and elasticity required for normal structure and function of the skin may be attributed to the network of elastic tissue. Advances in our understanding of elastic tissue physiology provide a foundation for studying the pathogenesis of elastic tissue disorders. Many acquired disorders are nevertheless poorly understood due to the paucity of reported cases. Several acquired disorders in which accumulation or elastotic degeneration of dermal elastic fibers produces prominent clinical and histopathologic features have recently been described. They include elastoderma, linear focal elastosis, and late-onset focal dermal elastosis and must be differentiated from better-known disorders, among them acquired pseudoxanthoma elasticum, elastosis perforans serpiginosa, and Favré-Racouchot syndrome. Learning objective At the conclusion of this learning activity, participants should understand the similarities and differences between acquired disorders of elastic tissue that are characterized by an increase in elastic tissue, as well as the spectrum of solar elastotic dermatoses.     

Cigarette smoking-associated elastotic changes in the skin.

BACKGROUND: Clinical features of the skin in persons who smoke include increased wrinkling, gauntness, and discoloration that has been termed smoker's face. The histologic changes in the sun-exposed skin of these patients have not been previously elucidated. OBJECTIVE: The purpose of this study was to assess the amount of elastosis in the sun-exposed skin of smokers and nonsmokers. METHODS: We evaluated the skin from the forehead and cheeks of 17 smokers and 14 nonsmokers for the presence of elastosis. With the use of a computer-generated analysis of tissue sections at 4 different levels, the amount of elastotic material was expressed as an average percent of the field staining for elastic tissue. Patients were also evaluated for the presence of other malignancies, arsenic and radiation exposure, and previous skin cancers. RESULTS: There was a significantly greater amount of elastosis (P < .05) in the skin of patients who smoked compared with those patients who did not. No significant differences were found between the 2 groups with regard to the other parameters evaluated. CONCLUSION: Cigarette smoking is associated with an increase in elastosis, which may contribute to the clinical features of "smoker's face."     

Elastosis in chronic radiodermatitis AN ULTRASTRUCTURAL STUDY

The electron microscopic study of six cases of chronic radiodermatitis from sun-exposed and unexposed skin, confirms the observation of elastosis previously described with light microscopy. The pathological findings are comparable with those found in actinic elastosis; increased width of the fibres, irregularity of their shape, increased density and granularity of the microfibrils and holes with many lobes in the matrix. The findings may be due to transformation of elastic fibres into elastotic fibres or the formation of dystrophic elastotic fibres by dermal fibroblasts.     

The Elastic Tissue of the Skin

In order to separate the changes of actinic damage from those of simple aging, we studied the elastic fibers in low and high sun-exposed skins of normal subjects at different ages. Low sun-exposed skin shows chronologic aging lesions only. These begin at age 30 with a disappearance of oxytalan fibers and with some abnormalities in the reticular and deep dermis; at age 40, aging changes are established: no oxytalan fibers, marked abnormalities, and lysis of elaunic and elastic fibers. In high sun-exposed skin, age-related lesions also occur but are associated with more or less precocious elastotic degeneration in reticular and deep dermis. Both types of aging fibers are revealed by the antielastin antibody HB 8, disappear with elastase, but resist collagenase. Actinic elastosis clearly originates from elastin. The two types of change differ in electron microscopic appearance: with spontaneous aging, elastic fibers are disintegrated (loose and porous fibers); in actinic damage, elastotic fibers are thicker and have accentuated microfibril dense masses. The age-associated lesions could be due to the activity of protease of fibroblastic origin whereas the elastotic degeneration is probably due to the actinic stimulation of fibroblasts.     

Bullous solar elastosis

Solar elastosis is a recognized manifestation of chronic sun exposure affecting mainly Caucasian skin. Recognizable clinical manifestations of solar elastosis include cutis rhomboidalis nuchae, Favre-Racouchot syndrome, actinic comedonal plaque, nodular forms such as elastomas, elastic nodule of the ear and elastotic bands, collagenous plaques of the hand, and colloid milia. We report two patients with an unusual presentation of vesicular lesions clinically and histopathologically situated in zones of severe solar elastosis that has been previously referred to as bullous solar elastosis.     

Immunohistochemical studies of amyloid P component in disorders of cutaneous elastic tissue

Distinctive abnormalities in the immunofluorescence/immunoperoxidase staining pattern of dermal elastic tissue were observed with antibodies to serum amyloid P component (SAP) in solar elastosis, lupus erythematosus, porphyria and pseudoxanthoma elasticum, and resembled those seen with conventional elastic tissue stains. Electron microscopy of elastotic skin revealed the presence of vacuotated disintegrating elastic fibres. Islands of amorphous microfibrillar material were surrounded by a rim of specific staining with anti-SAP, indicating an elastic tissue origin; there was no evidence for the involvement of collagen fibres in the formation of elastotic material. Immunohistochemical staining with anti-SAP, a marker for elastic fibre microfibrils, is a useful method for the investigation of cutaneous elastic tissue disorders.     

Physical properties of the photodamaged human skin dermis: Rougher collagen surface and stiffer/harder mechanical properties

Fragmentation of collagen fibrils and aberrant elastic material (solar elastosis) in the dermal extracellular matrix (ECM) is among the most prominent features of photodamaged human skin. These alterations impair the structural integrity and create a dermal microenvironment prone to skin disorders. The objective of this study was to determine the physical properties (surface roughness, stiffness and hardness) of the dermal ECM in photodamaged and subject‐matched sun‐protected human skin. Skin samples were sectioned and analysed by histology, atomic force microscopy and nanoindentation. Dermal ECM collagen fibrils were more disorganized (ie, rougher surface), and the dermal ECM was stiffer and harder, in photodamaged forearm, compared to sun‐protected underarm skin. Cleavage of collagen fibrils in sun‐protected underarm dermis by recombinant human matrix metalloproteinase‐1 resulted in rougher collagen fibril surface and reduced dermal stiffness and hardness. Degradation of elastotic material in photodamaged skin by treatment with purified neutrophil elastase reduced stiffness and hardness, without altering collagen fibril surface roughness. Additionally, expression of two members of the lysyl oxidase gene family, which insert cross‐links that stiffen and harden collagen fibrils, was elevated in photodamaged forearm dermis. These data elucidate the contributions of fragmented collagen fibrils, solar elastosis and elevated collagen cross‐linking to the physical properties of the dermal ECM in photodamaged human skin. This new knowledge extends current understanding of the impact of photodamage on the dermal ECM microenvironment.     

光线性弹性组织变性形成机制的研究进展

光线性弹性组织变性的形成机制包括弹性纤维变性和堆积.弹性纤维的变性涉及活性氧簇增多、成纤维细胞的损伤和衰老、弹性蛋白酶和基质金属蛋白酶生成增加.堆积机制主要包括成纤维细胞合成弹性纤维增多、弹性蛋白分别与溶菌酶和皮肤来源的抗白细胞蛋白酶结合抵抗弹性蛋白酶降解、组织蛋白酶K活性降低等.组织蛋白酶K在光线性弹性组织变性堆积中的作用机制可能是未来研究光老化的新方向.     

Immunohistochemical study of chronological and photo-induced aging skins using the antibody raised against D-aspartyl residue-containing peptide

BACKGROUND: Biologically uncommon D-aspartyl residues have been reported in the elderly tissues such as tooth, eye lens, aorta, and brain. We have previously prepared the antibody against D-aspartyl residue-containing peptide and found that it reacted with elastotic material of actinic elastosis. METHODS: Immunoreactivity of the normal skins obtained from sun-exposed and sun-protected skins of varied ages with this antibody was studied. RESULTS: In the sun-exposed skins, the antibody showed negative reaction with the skin specimens of young donors, whereas it reacted with elastotic materials of actinic elastosis of the elderly. In the sun-protected skins, the antibody recognized elastic fiber-like structures and inner layer of vessels found from the mid to lower dermis of old donors but showed no positive reaction to skin specimens of young donors. CONCLUSIONS: The results suggest that the antibody is a potent marker for chronological and ultraviolet (UV)-induced skin aging. Unusual eosinophilic bodies seen in the superficial dermis in the sun-exposed area of the elderly skins were also immunoreactive with the antibody, suggesting that the eosinophilic bodies resulted from UV-induced skin damage.     

Immunochemistry of elastotic material in sun-damaged skin

The nature of elastotic material in sun-damaged human skin was investigated by indirect immunofluorescence. Antibodies were used against the following components of the dermis: type I and type VI collagens, aminopropeptide of type I and type III procollagens, fibronectin, elastin, microfibrillar proteins, and basement membrane represented by the 7S domain of type IV collagen, laminin, and nidogen. The elastotic material exhibited marked fluorescence for elastin and microfibrillar proteins which codistributed with fibronectin. The presence of type I and VI collagens and procollagen type III were demonstrated to a lesser extent within the elastotic material. These results suggest that solar elastosis is primarily derived from elastic fibers and not from preexisting or newly synthesized collagens.     

Solar damage in skin tumors: quantification of elastotic material.

BACKGROUND: The elastotic changes of the dermis are thought to be the primary indicator of the cumulative sun exposure of the dermis. The changes of elastotic material have been evaluated by several previous methods, but these did not quantitatively measure the amount of elastic tissue. OBJECTIVE: The purpose of this study was to quantify dermal elastosis and to assess the significance of sun exposure in the pathogenesis of nonmelanomatous skin tumors such as basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and Bowen's disease (BD). METHODS: Ninety-nine sections from biopsy specimens of histopathologically proven BCC, SCC and BD were stained with Verhoeff-van Gieson stains. We studied the amount of elastotic material adjacent to the tumor by image analysis. RESULTS: There was a 3- to 4-fold increase in the amount of elastotic material in BCC and SCC compared to the sun-exposed skin of normal controls (p < 0.0001). The amount of elastotic material was increased 1.3 times in BD as compared with the nonexposed skins of normal controls (p < 0.01). CONCLUSION: We demonstrated a quantitative relationship between cumulative solar exposure and skin cancer such as SCC, BCC and BD.     

Expression of elastin-related proteins and matrix metalloproteinases in actinic elastosis of sun-damaged skin

Abstract Actinic elastosis is characterized by an accumulation of elastotic material in the upper dermis and is considered to be a manifestation of ultraviolet-induced skin aging. To compare the structural components of the elastotic material in actinic elastosis with those in normal skin, skin specimens were stained with antibodies raised against various elastin-related proteins. Elastotic materials exhibited a strong reaction to the antibodies for elastin, microfibril-associated glycoprotein-1 (MAGP-1), MAGP-4, matrix metalloproteinase 1 (MMP-1), MMP-2 and MMP-3, but a diminished reaction to anti-MMP-9 antibody. Fibroblast cell lines from the upper dermis of affected and unaffected skin were established, and the mRNA levels of MMPs were determined. MMP-1 and -2 mRNA levels were found to be elevated approximately twofold in the fibroblasts from actinic elastosis. Since MMP-1 and -2 are considered to be major enzymes involved in the degradation of matrix components, the accumulation of elastotic materials in actinic elastosis may be related to the degradation process. Received: 3 March 1999 / Received after revision: 26 August 1999 / Accepted: 6 September 1999     

Cross-Linking of Elafin/SKALP to Elastic Fibers in Photodamaged Skin: Too Much of a Good Thing?

Muto et al. report that UVA light induces the expression of elafin, a potent elastase inhibitor, in skin fibroblasts. Elafin binds to elastic fibers by transglutaminase-mediated cross-linking and protects against proteolytic breakdown. Decreased degradation could contribute to accumulation of elastotic material in photodamaged skin. Elastase and its locally produced inhibitors play a role in actinic elastosis.     

Digital papular calcific elastosis: a histopathological, histochemical and ultrastructural study of 20 patients

In 1960, 5 patients were reported with a condition termed "degenerative collagenous plaques of the hands". Ultraviolet light and chronic pressure seem to be the inciting factors. Clinically, it is characterized by keratotic, translucent papules, in linear array, on the radial border of the hands. Histology shows hyperkeratosis and dermal elastosis. The current study documented the histopathological, histochemical and ultrastructural features of 20 patients with this condition and considered the differential diagnoses. The findings were in accordance with those of previous studies, but peculiar, basophilic elastotic masses (BEMs), were a prominent finding. Ultrastructurally, elastic tissue appeared in the form of degenerated non-fragmented and fragmented elastic fibres, degenerated fibres showing foci of increased density, with or without a fibrillar component and as amorphous, structureless material. BEMs arose almost exclusively from degenerated elastic tissue and contained calcium. Disintegrated collagen may be incorporated in the amorphous material and, subsequently, form a minor part of BEMs. Solar elastosis, and its variants, show some similarity to degenerative collagenous plaques of the hands, but lack the constant presence of these calcified angular elastotic masses. BEMs show resemblance to elastic globes, and elastotic bodies found in elastotic nodules of the anthelix and cartilage-hair hypoplasia. In the clinical setting of "degenerative collagenous plaques of the hands", BEMs seem to be unique and due to their extensive presence serve as a non-specific marker for this condition. Digital papular calcific elastosis therefore seems to be more appropriate nomenclature.     

The surface structural alterations of elastic fibers and elastotic material in solar elastosis: a scanning electron microscopic study

The surface structure of altered elastic libers and elastotic material in solar elastosis has been described using a scanning electron microscope. There were 3 different areas in the dermis, depending on the degree of changes in elastic fibers: areas of (1) normal-looking fibers, (2) thick, cylindrical fibers, and (3) a large mass of markedly changed fibers. They were mainly located in the deep, middle, and upper dermis, respectively. The normal-looking fibers were the same as the normal elastic fiber. The thick, cylindrical fibers showed various findings ranging from relatively normal to heavily damaged surface. The large mass was composed of a cord-like element and a fine net-like one. There was a transition between the thick, cylindrical fibers and the large mass. It is suggested that the thick, cylindrical fiber is an early event and the mass is more damaged, as one of the elaslolic changes in solar elastosis. It is also suggested thai the thick, cylindrical fiber corresponds to the fibrous form ami the mass to the amorphous form of the elastotic material.     

Chronic sun exposure alters both the content and distribution of dermal glycosaminoglycans

Summary Chronic sun exposure leads to structural and functional alterations in exposed skin. Photoageing is a process distinct from the changes taking place due to chronological ageing. Unique alterations in the dermal extracellular matrix occur as a result of photoageing and are responsible for many of these physiological changes taking place in sun-damaged skin. Accompanying the deposition of abnormal elastic tissue, or solar elastosis, are significant alterations in dermal glycosaminoglycans (GAGs). Accumulation of GAGs as a result of photoageing as demonstrated in both humans and animal models of photoageing seems almost paradoxical in view of the large amounts of GAGs present in the skin of newborns, making their skin well hydrated and supple, in sharp contrast to the weathered appearance of photoaged skin. We investigate the relative GAG content of photoaged skin using immunoperoxidase stains specific for hyaluronic acid and chondroitin sulphate, and determine the location of these GAGs using confocal laser scanning microscopy. Our results demonstrate significant increases in GAG staining in sun-damaged vs. sun-protected skin from the same individuals, as measured by computer-based image analysis. Furthermore, confocal laser scanning microscopy reveals that the increased dermal GAGs in sun-damaged skin are deposited on the elastotic material of the superficial dermis of photodamaged skin, and not between collagen and elastic fibres as in normal skin. The abnormal location of GAGs on these fibres may explain the apparent paradoxical weathered appearance of photodamaged skin despite increased GAGs.     

Elastic tissue changes in generalized granuloma annulare

The histological picture in granuloma annulare (GA) is well defined. The types of infiltrate and the changes in collagen and elastic tissue have been repeatedly described. This is a preliminary study focused on the elastic tissue changes in lesions of generalized GA. Biopsies from four patients were studied. Specimens of involved and uninvolved skin from both exposed and unexposed parts of the body were compared. Changes of actinic elastosis in the papillary dermis in each patient in different stages were observed only in the exposed skin. The typical GA infiltrate was located beneath, in the upper mid-dermis. In the zone of the infiltrate in all specimens--exposed and unexposed--with no regard to the severity of actinic elastotic changes, absence or a marked reduction of elastic material was noted with engulfment of elastic remnants in giant cells. Giant cells with phagocytosis of elastotic material were mostly located on the periphery of the granuloma in the upper as well as in the deeper portion, where elastic fibers were still present. This might support the suggestion that degenerating elastic fibers promote the granulomatous reaction that leads to the formation of granuloma annulare.     

Electron microscopic study of the colloid-like substance in solar elastosis

We have made electron microscopic studies on the elastotic material of solar elastosis which developed in cutis rhomboidalis nuchae taken from 10 males, 50-83 years of age. It was revealed that this material of the cutis rhomboidalis nuchae contained a colloid-like substance consisting of both a fine granular and an amorphous component. The colloid-like substance closely resembled that which is seen in the adult-type colloid milium, and could not be distinguished from it under light microscopy. In view of the morphological similarity at the ultrastructural level between the elastotic material and the colloid-like substance, it was proposed that normal elastic fibers can change into elastotic material and then further degenerate into the colloid-like substance, eventually becoming the typical colloid substance seen in colloid milium.