Plump endothelial cells integrated into pre-existing venules contribute to the formation of 'mother' and 'daughter' vessels in pyogenic granuloma: possible role of galectin-1, -3 and -8.

INTRODUCTION: Pyogenic granuloma (PG) is a reactive inflammatory vascular lesion of the skin and mucous membranes, characterised by the presence of enlarged venules and seamed and seamless capillaries with plump endothelial cells (EC), and numerous macrophages. EC activation upregulates the synthesis of galectins and induces their translocation to the EC surface promoting angiogenesis and lymphangiogenesis, particularly galectin-1 (Gal-1), Gal-3 and Gal-8. However, the presence and distribution of Gal-1, -3 and -8, as well as their implications in the pathogenesis of PG, has not been considered. MATERIALS AND METHODS: Eight biopsies from patients diagnosed with PG were selected. The presence of PECAM-1/CD31, IL-1ß, VEGF-C, VEGFR-2, VEGFR-3, integrin ß1, CD44, fibronectin and Gal-1, -3 and -8 was assessed by immunofluorescence staining using confocal laser scanning microscopy. RESULTS AND DISCUSSION: Immunostaining revealed that these molecules were present in the enlarged venules with plump ECs, in some macrophages and other immune cells. We propose that macrophages release VEGF-A and VEGF-C inducing VEGFR-2/VEGFR-3 expression and activation, leading macrophages to transdifferentiate into plump ECs that might integrate into pre-existing venules, contributing to the formation of enlarged venules with transluminal bridges and capillaries. EC activation, induced by certain cytokines, has been shown to stimulate galectin expression and changes in the cellular localisation through association and activation of specific EC surface glycoproteins. Therefore, it is plausible that Gal-1, -3 and -8, acting in a concerted manner, could be mediating the transdifferentiation of macrophages into plump ECs and facilitating their migration and incorporation into the new vessels. LAY SUMMARY: In this study, immunostaining of pyogenic granuloma (PG) tissue sections showed immunoreactivity for PECAM-1/CD31, IL-1ß, VEGF-C, VEGFR-2 and VEGFR-3, and galectin-1, -3 and -8 in enlarged venules with plump endothelial cells (EC), as well as in some macrophages and other immune cells. Interestingly, enlarged and thin-walled transient vessels lined by PECAM-1/CD31 and VEGFR-2 immunopositive ECs that form from pre-existing normal venules in response to VEGF-A (called 'mother' vessels [MV]) and that undergo intraluminal bridging evolving into various types of capillaries (called 'daughter' vessels [DV]) have been observed in benign and malignant tumours, in physiological and pathological angiogenesis as well as in vascular malformations, suggesting an important role for VEGF-A and VEGFR-2 in such a process. However, it is not only the mechanisms by which the MVs evolve in different types of DVs that remains to be elucidated, but also whether the cells that form intraluminal bridges proceed from locally activated ECs or whether they are derived from bone marrow precursors or from resident macrophages.Given that the formation of homodimers by Gal-1 and Gal-8 and pentamers by Gal-3 to generate gal-glycan lattices at the cell surface and in the extracellular space has been shown, it is possible that in PG tissue Gal-1, -3 and -8, through their binding partners, form a supramolecular structure at the surface of ECs and plump ECs, macrophages and in the extracellular space that might be mediating the transdifferentiation of macrophages into plump ECs and facilitating the migration and incorporation of these cells into the pre-existing venules, thus contributing to the formation of MVs and DVs.

Galectin-1 and Galectin-3 and Their Potential Binding Partners in the Dermal Thickening of Keloid Tissues.

Keloids are defined histopathologically as an inflammatory disorder characterized by exhibiting numerous fibroblasts, abnormal vascularization, increased number of proinflammatory immune cells as well as uncontrolled cell proliferation, and exacerbated and disorganized deposition of extracellular matrix (ECM) molecules. Importantly, many of these ECM molecules display N- and O-linked glycan residues and are considered as potential targets for galectin-1 (Gal-1) and galectin-3 (Gal-3). Nevertheless, the presence and localization of Gal-1 and Gal-3 as well as the interactions with some of their binding partners in keloid tissues have not been considered. Here, we show that in the dermal thickening of keloids, versican, syndecan-1, fibronectin, thrombospondin-1, tenascin C, CD44, integrin ß1, and N-cadherin were immunolocalized in the elongated fibroblasts that were close to the immune cell infiltrate, attached to collagen bundles, and around the microvasculature and in some immune cells. We also show that Gal-1 and Gal-3 were present in the cytoplasm and along the cell membrane of some fibroblasts and immune and endothelial cells of the dermal thickening. We suggest that Gal-1 and Gal-3, in concert with some of the ECM molecules produced by fibroblasts and by immune cells, counteract the inflammatory response in keloids. We also proposed that Gal-1 and Gal-3 through their binding partners may form a supramolecular structure at the cell surface of fibroblasts, immune cells, endothelial cells, and in the extracellular space that might influence the fibroblast morphology, adhesion, proliferation, migration, and survival as well as the inflammatory responses.

Mucin1 expression in focal epidermal dysplasia of actinic keratosis.

BACKGROUND: Actinic keratoses (AKs) are generally considered as premalignant skin lesions that can progress into squamous cell carcinoma (SCC) in situ and invasive SCC. However, its progression to SCC is still matter of debate. A transmembrane glycoprotein that contributes to the progression of certain premalignant and malignant lesions is mucin1 (MUC1). Nevertheless, their functions in the skin lesions are not yet fully clear. Therefore, the aim of this study is to ascertain whether MUC1 is present in the focal epidermal dysplasia of AK. METHODS: Fourteen skin biopsies from patients diagnosed with AK were selected. They were classified according to the degree of dysplasia in keratinocyte intraepidermal neoplasia (KIN) I, KIN II, and KIN III. In five biopsies the three degrees were present, in two biopsies both KIN I and KIN II, in four biopsies only KIN I, and in three biopsies only KIN III. The presence of MUC1 was assessed by immunofluorescence staining using confocal laser scanning microscopy. RESULTS: Immunostaining revealed that MUC1 was present over the entire cell surface of only a few atypical basal keratinocytes confined to the lower third of the epidermis (KIN I). While in KIN II where atypical keratinocytes occupy the lower two thirds, MUC1 was localized at the apical surface of some atypical keratinocytes and over the entire cell surface of some of them. Interestingly, in KIN III where the atypical keratinocytes extend throughout the full thickness, MUC1 was localized at the apical surface and over the entire cell surface of many of these cells. Conversely, MUC1 expression was not detected in the epidermis of normal skin. CONCLUSIONS: Our findings suggest that the expression of MUC1 in AK would be induced by alteration of keratinocyte stratification and differentiation and associated to the degree of dysplasia rather than the thickness of the epidermis.

Presence of MUC1 in the epidermal thickening of psoriatic plaques.

Mucin 1 (MUC1) is a transmembrane glycoprotein that protects epithelial cells from injury caused by external stimuli. In addition to this role, MUC1 is involved in cell-cell adhesion, proliferation, motility, invasion and survival. In epithelial cells, MUC1 expression is regulated by binding of TNFα to TNFR1 and activation of the NFκB pathway. In human skin, MUC1 is not expressed in normal epidermis but rather in pre-malignant and malignant conditions. Nevertheless, the expression of MUC1 and its implication in psoriasis vulgaris has not been considered. Here, we show that MUC1 was present in the epidermis of psoriatic plaques observed in 11 biopsies from patients diagnosed with psoriasis vulgaris which were compared with 5 normal human skin. Interestingly, MUC1 in addition to being localized at the apical surface of some suprabasal keratinocytes, was also localized over the entire cell surface of some of these cells and some basal keratinocytes. Conversely, no MUC1 immunoreactivity was detected in the epidermis of normal skin. Additionally, we demonstrated that activated TNFR1, c-Src, IKKα/ß and p50/p65 were present in the epidermal thickening. This study demonstrates the presence of MUC1 in psoriatic plaque and suggests a possible role for MUC1 during the motility, migration and survival of human keratinocytes, where activated TNFR1, c-Src and NFκB seem to be required.

Endothelial-mesenchymal transition occurs during embryonic pulmonary artery development.

Pulmonary vascular remodeling is a process generally associated with pulmonary hypertension that involves intimal thickening, medial hyperthrophy, and plexiform lesions. Morphological studies during pulmonary hypertension have indicated that intimal thickening consists of immature smooth muscle cells (SMCs) associated with determined extracellular matrix components, suggesting an important role for these cells in vascular lesions. Controversy exists regarding the nature and origin of the cells conforming the intimal thickenings. In this study, the authors characterized the in vivo phenotype of the cells located in the pulmonary artery wall during the advanced stages of chicken embryo development and examined whether intimal thickenings are present in such stages. Immunolabeling of cryosections demonstrated presence of intimal thickenings composed of mesenchymal cells that may arise from the endothelium. These cells persist either as nonmuscle throughout the development, or possibly convert to cells expressing alpha -smooth muscle actin (alpha-SM actin). To determine whether pulmonary endothelial cells undergo a transition to mesenchymal cells, the authors used pulmonary artery explants from 10- to 11-day-old chicken embryos and found that explanted endothelial cells detached from the monolayer and acquired mesenchymal characteristics. Some of these cells maintained immunoreactivity for von Willebrand factor (vWF), whereas other jointly lost vWF and gained alpha -SM actin expression (transitional cells), suggesting conversion to SMCs. Therefore, these findings strongly support the authors' in vivo observations and demonstrate that embryonic pulmonary endothelial cells undergo a transition to mesenchymal cells and participate in intimal thickening formation and pulmonary vascular remodeling.

Fractura lujación hueso grande: Reporte de un caso. (Síndrome escafoides hueso grande de Fenton) / Fracture-luxacion of great bone: Report of a case (Fenton's syndrome)

La presente comunicación trata sobre un caso de fractura lujación de hueso grande acompañado de fractura de escafoides carpiano, caso raro e importante por no haber sido diagnosticado hasta 5 semanas después de la lesión y cuya evolución luego de un año del tratamiento es satisfactoria

Fracturas del tercio distal de radio: análisis comparativo entre un tutor externo nuevo y placas atornilladas / Distal fractures of radius: comparative analysis between a new external tutor and screws plate

La presente comunicación tiene como finalidad mostrar las utilidades de un nuevo tutor externo, sencillo, versátil y de fácil adquisición y confección en el interior de nuestro país,para utilizar en el tratamiento las fracturas del tercio distal del radio y en comparación con uno de los mejores métodos de tratamiento actual como son las placas atornilladas de pequeños fragmentos. Para este análisis se estudiaron solamente fracturas tipo B y C según la clasificación AO, pues otras eran suceptibles de tratamiento ortopédico. El tutor propuesto ofrece resultados muy similares a las placas atornilladas, pero tiene la ventaja de su fácil confección y se evita el problema de suministros internacionales que en algunas oportunidades no son seguros, además de favorecer las industrias regionales