Biological evaluation of a new C-xylopyranoside derivative (C-Xyloside) and its role in glycosaminoglycan biosynthesis

The mechanical properties of skin are determined primarily by the extracellular matrix of the dermis. These mechanical and biological properties change significantly as a function of age. Key components of the extracellular matrix are proteoglycans, which are molecules composed of a core protein and covalently attached glycosaminoglycans. Proteoglycans and their constituent glycosaminoglycans are involved in many biological processes which are important for dermal function, such as proper formation of the collagen network. A recently developed compound, C-xylopyranoside derivative (C-Xyloside), was designed to mimic β-xylosides, which are known initiators of glycosaminoglycan biosynthesis. C-Xyloside was found, by several criteria, to act like β-xylosides, such as in the eliciting of an increase in glycosaminoglycan synthesis by human dermal fibroblasts in culture. This increase may lead to the preservation of matrix integrity and thereby contribute to the firmness of skin. Thus, C-Xyloside may be useful in improving the quality of skin.     

Patterns of glycosaminoglycan/proteoglycan immunostaining in human skin during aging.

Proteoglycans and their component glycosaminoglycans are involved in such cell-cell and cell-matrix interactions as cell adhesion and migration, processes that are essential for embryonic and fetal development. As definitive organs such as skin emerge, structurally different proteoglycans partition into highly defined compartments. In skin, these compartments correspond to morphologically and functionally distinct layers. However, during the normal aging process, the relative amounts of structurally distinct proteoglycans apparently varies independently in each of these layers. This was demonstrated, in an indirect immunocytochemical study, through the use of monoclonal antibodies that detect structurally distinct domains in glycosaminoglycan chains of proteoglycans. Using samples of normal human skin obtained from individuals ranging in age from 20 weeks of gestation to 98 years of age, we determined that a common distribution pattern existed in skin. The epidermis contained chondroitin 4- and keratan sulfates, the basal lamina was the only layer that contained chondroitin 6-sulfate, the papillary and reticular dermis contained principally dermatan sulfate. In addition, antibodies that recognize native domains in chondroitin sulfates identified proteoglycan subsets that partitioned into distinct layers. An important new finding was that the relative amounts of specific types of glycosaminoglycans varied in an age- and layer-dependent manner. In the epidermis there was a notable increase in keratan sulfate beginning at age 50. Chondroitin 6-sulfate, found principally in the basal lamina, decreased after age 60. In the papillary dermis, the amount of dermatan sulfate increased after age 50, whereas the amount of novel chondroitin sulfate epitope, detected by antibody 4C3, decreased with age. Thus, age-related changes in proteoglycan distribution exist and correlate with morphologic and functional changes that occur in the intrinsic process of aging in human skin.     

Immunohistochemical studies on proteoglycan expression in normal skin and chronic ulcers

BACKGROUND: Proteoglycans (PGs) represent a large family of complex molecules. They are found either as integral membrane components or constituents of the extracellular matrix. Their protein backbones are linked to different glycosaminoglycans, such as dermatan-, chondroitin-, keratan- or heparan sulphate. The molecules have specific functions during developmental processes as well as in diseases, such as cancer and inflammation. OBJECTIVES: The expression patterns of various cell-associated heparan and chondroitin/dermatan-sulphate PGs in human skin and chronic venous ulcers were investigated. METHODS: Tissue sections from 11 patients with chronic venous ulcers were used in this study. Monoclonal antibodies were used for detection of the proteoglycans syndecan-1, -2 and -4, glypican, CD44 and perlecan. RESULTS: The different PGs exhibited individual staining patterns. Syndecan-1 and -4 and glypican expression in chronic ulcers differed from the staining in normal skin. Whereas the expression of syndecan-4 and glypican in intact skin was mostly in the pericellular regions of keratinocytes, the epidermal cells from the wound edge contained mostly intracellular PGs. In the wound edge, syndecan-4 was predominantly expressed by epidermal basal layer cells. Syndecan-1 was less expressed at the epidermal wound margins. PGs bind growth factors, regulate proteolytic activity and act as matrix receptors. CONCLUSIONS: The altered expression patterns of glypican and syndecan-1 and -4 in chronic ulcers reflect their possible roles during inflammation and cell proliferation. Hence, analysis of PG expression should be of interest in future studies on normal as well as defective wound healing.     

A new C-xylopyranoside derivative induces skin expression of glycosaminoglycans and heparan sulphate proteoglycans

Severe structural changes, including deterioration of the mechanical properties of the dermis, occur during skin aging. It is well known that the degradation of the extracellular matrix contributes to the physical changes in aged skin. Whereas many studies have been devoted to age-related alterations of collagen fibrils, far less attention has been paid to another major family of extracellular matrix components, the glycosaminoglycans (GAGs) and proteoglycans (PGs). Heparan sulphate-proteoglycans, (HS-PGs), a subclass of the PG family that decreases during aging, regulate proliferation and proteolysis as well as matrix adhesion and assembly, and thus, may have important functions in skin. These PGs may represent important targets for dermo-cosmetology in fighting skin aging. The purpose of this study was to demonstrate the potential of a new C-xylopyranoside derivative (C-beta-D-xylopyranoside-2-hydroxy-propane simplified as C-Xyloside) to improve HS-PGs expression in human skin. In an organotypical model of corticosteroid atrophic human skin, characterized by a decrease of PGs expression, treatment with C-Xyloside improved expression of HS-PGs.     

Immature mast cells exhibit rolling and adhesion to endothelial cells and subsequent diapedesis triggered by E‐ and P‐selectin,VCAM‐1 and PECAM‐1

Please cite this paper as: Immature mast cells exhibit rolling and adhesion to endothelial cells and subsequent diapedesis triggered by E‐ and P‐selectin, VCAM‐1 and PECAM‐1. Experimental Dermatology 2010; 19: 424–434. Abstract: Mast cell numbers are markedly increased at sites of chronic inflammation. However, the underlying mechanisms of mast cell accumulation including mast cell progenitor trafficking remain to be identified in detail. Thus, the aim of this study was to identify the adhesion molecules involved in rolling, firm adhesion and transendothelial diapedesis of murine bone marrow‐derived cultured mast cells (BMCMC) as a model for immature mast cells. We could show that BMCMCs exhibit in vivo rolling on skin vessel walls and strong adhesion to skin endothelial cells (ECs) in vitro under static and flow conditions. Interestingly, interaction of BMCMC with the EC adhesion molecules E‐ and P‐selectin, vascular cell adhesion molecule‐1 (VCAM‐1) and platelet endothelial cell adhesion molecule‐1 (PECAM‐1) is required to mediate rolling and firm adhesion to ECs. The adhesion of BMCMCs to skin ECs is further enhanced by TNF, IL‐4, IL‐15 and vascular endothelial cell growth factor. Furthermore, BMCMCs exhibit directed and dose‐dependent transmigration across an endothelial barrier, mediated by a PECAM‐1‐dependent mechanism. Our results demonstrate that BMCMCs can undergo a tightly regulated extravasation cascade consisting of rolling on and adhesion to endothelium and followed by directed diapedesis and reveal selectins, VCAM‐1 and PECAM‐1 as required adhesion molecules. These processes may contribute to mast cell accumulation in chronic inflammatory skin diseases and reveal opportunities to modulate peripheral tissue numbers of mast cells.     

Expression of glycosaminoglycans and small proteoglycans in wounds: modulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu(2+)

Glycyl-histidyl-lysine-Cu(2+) is a tripeptide-copper complex previously shown to be an activator of wound healing. We have investigated the effects of glycyl-histidyl-lysine-Cu(2+) on the synthesis of glycosaminoglycans and small proteoglycans in a model of rat experimental wounds and in rat dermal fibroblast cultures. Repeated injections of glycyl-histidyl-lysine-Cu(2+) (2 mg per injection) stimulated the wound tissue production, as appreciated by dry weight and total protein measurements. This stimulation was accompanied by an increased production of type I collagen and glycosaminoglycans (assessed, respectively, by hydroxyproline and uronic acid contents of the chamber). Electrophoretic analysis of wound tissue glycosaminoglycans showed an accumulation of chondroitin sulfate and dermatan sulfate in control wound chambers, whereas the proportion of hyaluronic acid decreased with time. The accumulation of chondroitin sulfate and dermatan sulfate was enhanced by glycyl-histidyl-lysine-Cu(2+) treatment. The expression of two small proteoglycans of the dermis, decorin and biglycan, was analyzed by northern blot. The biglycan mRNA steady-state level in the chamber was maximal at day 12, whereas the decorin mRNA increased progressively until the end of the experiment (day 22). Glycyl-histidyl-lysine-Cu(2+) treatment increased the mRNA level of decorin and decreased those of biglycan. In dermal fibroblast cultures, the stimulation of decorin expression by glycyl-histidyl-lysine-Cu(2+) was also found. In contrast, biglycan expression was not modified. These results show that the expression of different proteoglycans in wound tissue are regulated in a different manner during wound healing. The glycyl-histidyl-lysine-Cu(2+) complex is able to modulate the expression of the extracellular matrix macromolecules differently during the wound repair process.     

Expression of proteoglycans and glycosaminoglycans in angiofibroma and fibrous plaque skin lesions from patients with tuberous sclerosis

Tuberous sclerosis complex (TSC) is a disorder of cell lineage, migration, proliferation and differentiation, characterized by the development of widespread benign hamartomas, which are particularly evident in hamartomatous lesions of the skin. The aim of this study was to investigate differences in gene expression of certain proteoglycans (PGs) and to characterize glycosaminoglycans (GAGs) in tissue specimens of normal skin, fibrous plaques and angiofibromas from patients with TSC. The expression of PG mRNA was determined by semiquantitative RT-PCR analysis. Total GAGs were isolated from tissue specimens after lipid extraction and extensive digestion with Pronase and DNase and characterized by treatment with GAG-degrading enzymes followed by electrophoresis on polyacrylamide gradient gels and cellulose acetate membranes. Normal skin specimens express versican, decorin and aggrecan and contain hyaluronic acid and dermatan sulphate. In angiofibroma specimens aggrecan is not expressed while versican splice variant with two EGF-like domains and decorin are downregulated. Furthermore, angiofibromas differ from normal skin in that they additionally contain keratan, heparan and chondroitin sulphates and do not contain dermatan sulphate. In fibrous plaque specimens gene expression of PGs was similar to that in normal skin, but with respect to GAGs, they contained a single acidic glycan population that did not share common structural features with known GAGs. The variations of the above ECM molecules between normal and TSC skin may be attributed to TSC-related mutations and, overall, support the TSC-associated pathological manifestations of cell migration, proliferation and differentiation.     

Expression of adhesion molecules in pagetoid reticulosis (Woringer-Kolopp disease)

Cell adhesion molecules play a critical role in lytnphocyte migration and homing. They convey tissue-specific homing properties to lymphocyte subsets and regulate the positioning of these subsets in the body. In a patient with pagetoid reticulosis. a rare form of cutaneous T-cell lymphoma characterized by extreme epitheliotropism. we examined the expression of adhesion molecules. The neoplastic T lymphocytes showed a strong expression of cutaneous lymphocyte antigen, a skinhoming receptor which interacts with E-selectin on skin endothelium. α^Eβ₇, an adhesion molecule interacting with E-cadherin on epithelial cells, was also expressed on tumour cells. These findings suggest that adhesion molecules are responsible for the unque growth pattern in pagetoid reticulosis. and for the clinical behaviour of the disorder.     

Adhesion of peripheral blood mononuclear cells and CD4+ T cells from patients with psoriasis to cultured endothelial cells via the interaction between lymphocyte function-associated antigen type 1 and intercellular adhesion molecule 1

BACKGROUND: The adhesion of CD4+ T cells to endothelial cells and their subsequent migration to skin tissue are essential to develop the psoriatic skin lesion. However, few studies have examined the role of adhesion molecules in the binding of T cells from patients with chronic plaque psoriasis to endothelial cells in vitro; thus, the adhesion molecules responsible for the development of skin lesions are still unclear. OBJECTIVES: To identify the responsible adhesion molecules in the interaction between CD4+ T cells in patients with chronic plaque psoriasis and cytokine-stimulated endothelial cells. METHODS: An in vitro adhesion assay between Calcein-labelled peripheral blood mononuclear cells (PBMC) and cytokine-stimulated human endothelial cultures, which exhibit a higher adhesion capacity to PBMC, was established, and the adhesion-inhibitory effects of a panel of antiadhesion molecule antibodies on the adhesion of PBMC from patients with psoriasis to endothelial cells were examined. Then, the inhibitory effects of selected antibodies acting on the interaction between CD4+ T cells from patients with psoriasis (purified by negative magnetic cell sorting) and cultured endothelial cells were examined. RESULTS: A significant increase (P < 0.01) in the adhesion of psoriatic PBMC to both endothelial cultures, human skin microvascular endothelial cells from adults (HMVEC-Ad) and human coronary arterial endothelial cells (HCAEC), compared with healthy PBMC, was demonstrated in our in vitro cell adhesion assay. Pretreatment of both endothelial cultures with tumour necrosis factor (TNF)-alpha (1000 U mL(-1)) induced the most frequent adhesion of PBMC from patients with psoriasis among the three inflammatory cytokines examined, i.e. TNF-alpha, interleukin-1beta and interferon-gamma [TNF-alpha-treated vs. nontreated: P < 0.001 (in both HMVEC-Ad and HCAEC)]. In both endothelial cultures treated with TNF-alpha, PBMC from patients with psoriasis exhibited significantly more frequent adhesion compared with those from healthy individuals (P < 0.001). The TNF-alpha-stimulated HMVEC-Ad, which exhibited the most frequent adhesion of PBMC, were selected for adhesion-inhibition experiments using monoclonal antibodies (mAbs) to adhesion molecules that are upregulated in psoriatic lesions, and the combination of antilymphocyte function-associated antigen type 1 (LFA-1) and anti-intercellular adhesion molecule 1 (ICAM-1) mAbs gave the greatest reduction of adhesion of PBMC from patients with psoriasis (approximately 69% reduction; P < 0.01). This combination of mAbs significantly reduced also the adhesion of CD4+ T cells from patients with psoriasis to TNF-alpha-stimulated HMVEC-Ad (approximately 62% reduction), compared with pretreatment with isotype control mAbs (P < 0.01). CONCLUSIONS: These findings indicate that the LFA-1/ICAM-1 interaction plays a major role in the adhesion of CD4+ T cells to endothelial cells and that TNF-alpha might play an important role for the induction of adhesion molecules on endothelial cells at psoriatic skin lesions.     

Histogenesis and possible mechanism of chondroid changes in mixed tumour of the skin: immunohistochemical evaluation of bone morphogenetic protein,glycosaminoglycans, keratin,vimentin and neuronal markers

The distribution of immunoreactivity of bone morphogenetic protein (BMP), the glycosaminoglycans chondroitin 4-sulphate (C4SPG), chondroitin 6-sulphate (C6SPG), dermatan sulphate (DSPG) and keratan sulphate proteoglycans (KSPG), cytokeratin (K8.12), vimentin, glial fibrillary acidic protein (GFAP), actin, desmin, S-100 protein and neuron-specific enolase (NSE) in mixed tumour of the skin was investigated using immunohistochemical methods using monoclonal (MoAb) and polyclonal antibodies (PoAb). A strong BMP immunoreactivity was found characteristically in outer tumour cells of tubuloductal structures and modified myoepithelial cells. Modified myoepithelial cells and chondroidally changed cells showed positive immunoreactivity for C4SPG, C6SPG and DSPG; and KSPG was more pronounced in the modified myoepithelial cells. Vimentin, S-100 protein, GFAP and NSE, but not actin and desmin, were distribute in the outer tumour cells and modified myoepithelial cells in chondroidally changed tissue. Two factors show that chondrogenesis in mixed tumour of the skin is associated with the modified myoepithelial cells through the activity of BMP and biosynthesis of glycosaminoglycans as matrix substance. First, outer or basal tumour cells in mixed tumour of the skin is characterized by the presence of positive immunoreactivity for BMP, KSPG, vimentin, cytokeratin K8.12, S-100 protein, GFAP and NSE, and second, there is a matrix of chondroidally changed tissue containing the reaction products of C4SPG, C6SPG, DSPF and KSPG.     

Proteoglycans in So-Called Cellulite

Glycosaminoglycans are a group of polysaccharide chains covalently linked to proteins to form proteoglycan molecules with high water-attracting properties. The ultrastructural localization of glycosaminoglycans in the so-called cellulite skin and in normal subjects was studied. Data show that there is increasing concentration of glycosaminoglycans in the cellulite skin, presumably leading to a rise in the amount of water retained in the skin in this disease.     

Skin fibroblast activity in pretibial myxoedema and the effect of octreotide (Sandostatin®) in vitro

The accumulation of glycosaminoglycans in the skin in pretibial myxoedema appears to be a response by local fibroblasts to a stimulating factor in the patient's serum, but the identity of the factor, its ability to stimulate skin fibroblasts as opposed to cultured thyroid cells, and the specificity of its effect to pretibial skin fibroblasts, are all controversial. We have studied fibroblasts cultured from the lesional skin of two women with pretibial myxoedema, and compared their proliferation and secretion of glycosaminoglycans with those of fibroblasts from the patients' forearms and from the forearm skin of two normal subjects. We found that in the presence of the patients' sera all six lines of fibroblasts secreted more glycosaminoglycans [205±21% (SD)] than with normal human sera (147±19%), or fetal calf serum (100%). Fibroblast proliferation showed the same pattern of differences: patients' sera 142±22%; normal human sera 116±9%, and fetal calf serum 100%. These experiments confirm the presence of a serum factor in pretibial myxoedema which is capable of stimulating the activity of skin fibroblasts in vitro, and show that its effects are not restricted to fibroblasts from pretibial skin or to those grown from the skin of the patients. Proliferation of normal fibroblasts cultured in medium supplemented with fetal calf serum was reduced by Sandostatin® (octreotide), but it failed to inhibit their secretion of glycosaminoglycans. In contrast, secretion of glycosaminoglycans by a patient's pretibial skin fibroblasts was almost completely inhibited by 1 mM minoxidil. In the presence of patients' sera Sandostatin® (0.1–10 μg/ml) reduced secretion of glycosaminoglycans by about 50%. Our data support the use of Sandostatin® in pretibial myxoedema, and suggest that it may suppress fibroblast glycosaminogly- can secretion within the skin via depletion of insulin-like growth factor or the blocking of its effect.     

Adhesion molecule mapping in normal human skin

Summary Adhesion molecules are a rapidly growing group of cell surface receptors providing cell-cell and cell-matrix interactions. Their physiological role in tissue homeostasis as well as cellular migration and differentiation is increasingly appreciated. In the present study we have analyzed the expression pattern of most adhesion molecules of the integrin family as well as of adhesion molecules belonging to the immunoglobulin superfamily in normal human skin. We provide evidence that expression of adhesion molecules in the various cutaneous cell systems follows a constant distribution. Moreover, the physiological mononuclear infiltrate of the skin also expresses a variety of adhesion molecules enabeling these cells to migrate or to reside within the skin. Furthermore, our results indicate that intercellular adhesion molecule-1 is not a prerequisite for lymphocyte epidermotropism as frequently stated. Our data provide a rational basis to analyze changing adhesion molecule expression in inflammatory and neoplastic skin diseases.     

E-selectin and vascular cell adhesion molecule-1 as critical adhesion molecules for infiltration of T lymphocytes and eosinophils in atopic dermatitis

To study the temporal and spatial relationship between infiltrating T-cell subsets or eosinophils and cell adhesion molecules on endothelial cells in skin lesions of atopic dermatitis (AD), we undertook immunohistochemical analysis using monoclonal antibodies against surface markers of T cells, eosinophil granule proteins and cell adhesion molecules. Predominant mononuclear cells in acute and chronic skin lesions were CDS, CD4 and CD45RO positive helper-inducer/memory T cells. Their number was significantly and strongly correlated with the intensity of E-selectin expression. Eosinophils and deposition of eosinophil-derived granule proteins such as eosinophil cationic protein (ECP), major basic protein (MBP) and eosinophil peroxidase (EPO) were found constantly in acute lesions and only occasionally in chronic lesions. The total number of immunoreactive eosinophils and deposits of MBP, EPO and ECP were significantly and strongly correlated with die staining intensity of VCAM-1. In chronic lesions significant reduction of VCAM-1 expression paralleled occasional infiltration of eosinophils. Our results demonstrate the possibility that E-selectin and VCAM-1 are the critical adhesion molecules for trafficking of memory T cells and eosinophils, respectively, into skin lesions of AD. Persistent expression of the adhesion molecules may be related to prolongation of the skin lesion in AD.     

Increased adhesion of fibroblasts from patients with scleroderma to extracellular matrix components: in vitro modulation by IFN-gamma but not by TGF-beta.

A characteristic feature of systemic scleroderma is fibrosis of the skin and eventually of internal organs resulting from an overproduction of collagen and other connective tissue components by the resident fibroblasts. The balance between the cells and the amount of the surrounding extracellular matrix is then altered. Because cellular metabolism depends to a large extent on cellular contacts and communications with connective tissue molecules, we have therefore investigated the interactions with extracellular matrix components of fibroblasts obtained from skin of patients affected with scleroderma. In comparison to fibroblasts from healthy skin, all fibroblasts from scleroderma patients had an increased adhesion capacity to collagens I, IV, VI, fibronectin, and laminin. In addition, whereas adhesion of control fibroblasts was stimulated by a pre-treatment with transforming growth factor-beta, adhesion patterns of scleroderma fibroblasts remained unchanged. However, pre-incubation of the cells with interferon-gamma decreased the adhesion of both scleroderma and control fibroblasts.     

Matricryptins and matrikines: biologically active fragments of the extracellular matrix

Numerous extracellular proteins and glycosaminoglycans (GAGs) undergo limited enzymatic cleavage resulting in the release of fragments exerting biological activities, which are usually different from those of the full‐length molecules. In this review, we define matrikines and matricryptins, which are bioactive fragments released from the extracellular matrix proteins, proteoglycans and GAGs and report their major biological activities. These fragments regulate a number of physiopathological processes including angiogenesis, cancer, fibrosis, inflammation, neurodegenerative diseases and wound healing. The challenges to translate these fragments from molecules biologically active in vitro and in experimental models to potential drugs are discussed in the last part of the review.     

银屑病患者血清和皮损中血管内皮细胞粘附分子的对比研究

目的 探讨银屑病患者血清和皮损中4种血管内皮粘附分子表达与银屑病疾病活动性之间的关系。方法 采用ELISA法检测36例银屑病患者治疗前后和36例健康人的血清中可溶性粘附分子（sICAM-1、sICAM-3、sVCAM-1、sELAM）的浓度。同时用ABC免疫组化染色技术检测了36例银屑病患者皮损和临床治愈处皮肤粘附分子（ICAM－1、ICAM－3、VCAM－1、ELAM）的表达情况。结果 与正常人相比，银屑病患者皮损部位4种粘附分子的原位表达呈明显上调（P＜0.005），同时患者血清中4种可溶性粘附分子浓度也明显升高（P＜0.001）。经治疗后银屑病患者皮损部位4种粘附分子的原位表达明显下调（P＜0.05），同时血清中4种可溶性粘附分子浓度比前也下降（P＜0.05）；血清中4种可溶性粘附分子的浓度与银屑病疾病活动严重指数（PASI）均呈正相关，但治疗前后sVCAM-1的水平上升和下降的幅度最大，且与PASI的相关性最好。结论 血管内皮细胞粘附分子参与银屑病的发病机制；患者血清中可溶性粘附分子浓度的升高可能与皮损部位血管内皮细胞上相应的粘附分子高表达有关；血清VCAM－1的水平可以作为反映银屑病疾病活动的一个新的敏感指标。     

Early events in skin appendage formation: induction of epithelial placodes and condensation of dermal mesenchyme

The formation of skin appendages represents a morphogenetic process through which a homogeneous system is converted into a patterned system. We have pursued molecules involved in the early placode induction and mesenchymal condensation stages of this process. We found that intracellular and extracellular signaling molecules collaborate to position the location of feather primordia and initiate mesenchymal condensations mediated by adhesion molecules. During the inductive stage, cells interact in a fashion best described by a reaction-diffusion mechanism. Thus in early feather morphogenesis, low level adhesion molecules drive cell interactions. The interactions were modulated by extracellular signaling molecules, which eventually increase the level of signaling molecules at sites of feather initiation and subsequently the level of adhesion molecules (Jiang et al, 1999a). These physico-chemical events lead to the formation of dermal condensations and epithelial placodes at sites of feather primordia, thus achieving the earliest and most fundamental events of skin appendage formation: induction.     

Los glicosaminoglicanos se encuentran implicados en la adherencia de Candida albicans y Malassezia spp. a queratinocitos,pero no a fibroblastos dérmicos

Background and objectiveSuperficial mycoses are some of the most common diseases worldwide. The usual culprits — yeasts belonging to the genera Malassezia and Candida — are commensal species in the skin that can cause opportunistic infections. We aimed to determine whether these yeasts use glycosaminoglycans (GAGs) as adhesion receptors to mediate binding to epithelial cells.Material and methodsIn keratinocyte and dermal fibroblast cultures, we used rhodamine B and genistein to inhibit GAG synthesis to study the role these molecules play in the adhesion of Candida albicans (C. albicans) and Malassezia species to cells. We also analyzed GAG involvement by means of enzyme digestion, using specific lyases.ResultsRhodamine B partially inhibited the adhesion of both fungi to keratinocytes but not to fibroblasts. Selective digestion of heparan sulfate enhanced the binding of Malassezia species to keratinocytes and of both fungi to fibroblasts. Chondroitin sulfate digestion decreased C. albicans adhesion to keratinocytes, but increased the adhesion of the filamentous forms of this species to fibroblasts.ConclusionsCell surface GAGs appear to play a role in the adhesion of C albicans and Malasezzia species to keratinocytes. In contrast, their adhesion to fibroblasts appears to be enhanced by GAG inhibition, suggesting that some other type of receptor is the mediator.