BMB activity defines refractory and competent hair follicle populations during the propagation of regenerative waves

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PLANEJAMENTO E GESTÃO DA MOBILIDADE EM GRANDES METRÓPOLES: Reflexões acerca das estratégias do São Paulo Convention & Visitors Bureau para o turismo de negócios e eventos em São Paulo

A partir de reflexões acerca do planejamento e da gestão do turismo com relação à mobilidade em grandes metrópoles, o presente artigo tem como objetivo analisar o processo histórico pelo qual o turismo de negócios e eventos se estabeleceu espacialmente em São Paulo e quais as estratégias adotadas pelo São Paulo Convention & Visitors Bureau (SPCVB), representante da iniciativa privada, diante das especificidades desse espaço urbano extremamente adensado. Para tal, foi realizado levantamento de dados históricos da gestão pública do turismo da metrópole e do SPCVB, bem como a analogia mundial da entidade, coleta de dados atuais por meio de material promocional e entrevista, a fim de estabelecer um panorama atual diante das dificuldades de mobilidade encontradas em uma metrópole mundial, como é o caso de São Paulo

Expression, but lack of calcium mobilization by high-affinity IgE Fcε receptor I on human epidermal and dermal Langerhans cells

: In atopic dermatitis (AD) patients, IgE molecules are demonstrated on the surface of Langerhans cells (LC). FcεRI molecules, which are present on the surface of LC in AD patients as well as normal individuals, are responsible for this binding. In this study, we have investigated phenotypic and functional characteristics of FcεRI on epidermal and dermal cell populations. Epidermal and dermal cell suspensions were prepared enzymatically with dispase followed by either trypsin or collagenase treatment, respectively. Peripheral blood basophils were negatively selected by excluding other leukocytes with surface marker staining. Consistent with previous reports, both peripheral blood basophils and epidermal LC were positively stained with anti FcεRI monoclonal antibody. In addition, an FcεRI positive population was demon-strated among dermal HLA-DR positive cells. These cells express significant amounts of HLA-DR molecules (DR Hi ) and co-express CD la molecules, which identifies them as LC-like dendritie APC of the dermis. No other FcεRI positive population was found in the other dermal DR Mid or DR populations, except for a minor DR lo population, presumably mast cells. To analyze whether these FcεRI molecules are signal transducing for LC, intracellular calcium mobilization after crosslinking of FcεRI was measured with How cytometry. Following crosslinking, peripheral blood basophils clearly increased intracellular calcium. On the other hand, neither normal epidermal LC nor dermal DR Hi CD Ia + cells changed their intracellular calcium level after FcεRI crosslinking. These data indicate that normal epidermal and dermal LC, but not basophils, are resistant to calcium flux following FcεRI engagement.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73771/1/j.1600-0625.1996.tb00129.x.pd

Fibroblasts Show More Potential as Target Cells than Keratinocytes in COL7A1 Gene Therapy of Dystrophic Epidermolysis Bullosa

Dystrophic epidermolysis bullosa (DEB) is an inherited blistering skin disorder caused by mutations in the type VII collagen gene (COL7A1). Therapeutic introduction of COL7A1 into skin cells holds significant promise for the treatment of DEB. The purpose of this study was to establish an efficient retroviral transfer method for COL7A1 into DEB epidermal keratinocytes and dermal fibroblasts, and to determine which gene-transferred cells can most efficiently express collagen VII in the skin. We demonstrated that gene transfer using a combination of G protein of vesicular stomatitis virus-pseudotyped retroviral vector and retronectin introduced COL7A1 into keratinocytes and fibroblasts from a DEB patient with the lack of COL7A1 expression. Real-time polymerase chain reaction analysis of the normal human skin demonstrated that the quantity of COL7A1 expression in the epidermis was significantly higher than that in the dermis. Subsequently, we have produced skin grafts with the gene-transferred or untreated DEB keratinocytes and fibroblasts, and have transplanted them into nude rats. Interestingly, the series of skin graft experiments showed that the gene-transferred fibroblasts supplied higher amount of collagen VII to the new dermal–epidermal junction than the gene-transferred keratinocytes. An ultrastructural study revealed that collagen VII from gene-transferred cells formed proper anchoring fibrils. These results suggest that fibroblasts may be a better gene therapy target of DEB treatment than keratinocytes

A Phenotypic Analysis of Involucrin-Membrane-Bound Ovalbumin Mice after Adoptive Transfer of Ovalbumin-Specific CD8⁺ T Cells

To investigate the mechanism of autoimmunity and peripheral tolerance in the skin, several transgenic mouse strains expressing membrane-bound ovalbumin (mOVA) as an epidermal self-antigen under the control of keratinocyte-specific promotors, such as keratin 5 and keratin 14, were employed in combination with adoptive transfer of CD8⁺ T cells from OT-I mice (OT-I T cells) that recognize an ovalbumin-derived peptide. However, these strains showed bodyweight loss and required additional inflammatory stimuli, such as γ-irradiation and tape-stripping, to induce skin inflammation. In this study, we generated a mouse strain expressing mOVA under the control of human involucrin promoter (involucrin-mOVA mice). In contrast to previous strains, involucrin-mOVA mice spontaneously developed skin inflammation after the transfer of OT-I T cells in the absence of external stimuli without significant bodyweight loss. We focused on the skin infiltration process of OT-I T cells and found that transferred OT-I T cells accumulated around the hair follicles in the early phase of skin inflammation, and in the later phase, the skin inflammation spontaneously resolved despite the remaining OT-I T cells in the skin. Our involucrin-mOVA mice will provide a promising tool to investigate the pathogenesis and the tolerance mechanisms of cytotoxic skin autoimmunity

Chitin, Chitinases and Chitinase-like Proteins in Allergic Inflammation and Tissue Remodeling

Chitin, the second most abundant polysaccharide in nature after cellulose, consist exoskeleton of lower organisms such as fungi, crustaceans and insects except mammals. Recently, several studies evaluated immunologic effects of chitin in vivo and in vitro and revealed new aspects of chitin regulation of innate and adaptive immune responses. It has been shown that exogenous chitin activates macrophages and other innate immune cells and also modulates adaptive type 2 allergic inflammation. These studies further demonstrate that chitin stimulate macrophages by interacting with different cell surface receptors such as macrophage mannose receptor, toll-like receptor 2 (TLR-2), C-type lectin receptor Dectin-1, and leukotriene B4 recepptor (BLT1). On the other hand, a number of chitinase or chitinase-like proteins (C/CLP) are ubiquitously expressed in the airways and intestinal tracts from insects to mammals. In general, these chitinase family proteins confer protective functions to the host against exogenous chitin-containing pathogens. However, substantial body of recent studies also set light on new roles of C/CLP in the development and progression of allergic inflammation and tissue remodeling. In this review, recent findings on the role of chitin and C/CLP in allergic inflammation and tissue remodeling will be highlighted and controversial and unsolved issues in this field of studies will be discussed