RESUMO
During growth and development, the skin expands to cover the growing skeleton and soft tissues by constantly responding to the intrinsic forces of underlying skeletal growth as well as to the extrinsic mechanical forces from body movements and external supports. Mechanical forces can be perceived by two types of skin receptors: (1) cellular mechanoreceptors/mechanosensors, such as the cytoskeleton, cell adhesion molecules and mechanosensitive (MS) ion channels, and (2) sensory nerve fibres that produce the somatic sensation of mechanical force. Skin disorders in which there is an abnormality of collagen [e.g. Ehlers-Danlos syndrome (EDS)] or elastic (e.g. cutis laxa) fibres or a malfunction of cutaneous nerve fibres (e.g. neurofibroma, leprosy and diabetes mellitus) are also characterized to some extent by deficiencies in mechanobiological processes. Recent studies have shown that mechanotransduction is crucial for skin development, especially hemidesmosome maturation, which implies that the pathogenesis of skin disorders such as bullous pemphigoid is related to skin mechanobiology. Similarly, autoimmune diseases, including scleroderma and mixed connective tissue disease, and pathological scarring in the form of keloids and hypertrophic scars would seem to be clearly associated with the mechanobiological dysfunction of the skin. Finally, skin ageing can also be considered as a degenerative process associated with mechanobiological dysfunction. Clinically, a therapeutic strategy involving mechanoreceptors or MS nociceptor inhibition or acceleration together with a reduction or augmentation in the relevant mechanical forces is likely to be successful. The development of novel approaches such as these will allow the treatment of a broad range of cutaneous diseases.
Assuntos
Derme/fisiopatologia , Epiderme/fisiopatologia , Dermatopatias/fisiopatologia , Animais , Doenças Autoimunes/metabolismo , Moléculas de Adesão Celular/metabolismo , Citoesqueleto/metabolismo , Derme/metabolismo , Epiderme/metabolismo , Regulação da Expressão Gênica , Humanos , Células Receptoras Sensoriais/metabolismo , Envelhecimento da Pele , Dermatopatias/metabolismoAssuntos
Humanos , Adenocarcinoma Sebáceo/diagnóstico , Adenocarcinoma Sebáceo/fisiopatologia , Adenocarcinoma Sebáceo/reabilitação , Carcinoma/diagnóstico , Carcinoma/fisiopatologia , Carcinoma/reabilitação , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/fisiopatologia , Lúpus Eritematoso Sistêmico/reabilitação , Epiderme/anormalidades , Epiderme/fisiopatologia , Epiderme/lesões , Epidermodisplasia Verruciforme/diagnóstico , Epidermodisplasia Verruciforme/fisiopatologia , Epidermodisplasia Verruciforme/reabilitação , Fibroma Ossificante/diagnóstico , Fibroma Ossificante/fisiopatologia , Fibroma Ossificante/reabilitaçãoAssuntos
Humanos , Dermatite Atópica/complicações , Dermatite Atópica/diagnóstico , Dermatite Atópica/reabilitação , Doenças das Glândulas Sebáceas/diagnóstico , Doenças das Glândulas Sebáceas/fisiopatologia , Doenças das Glândulas Sebáceas/reabilitação , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/fisiopatologia , Neoplasias Cutâneas/reabilitação , Urticária/complicações , Epiderme/anormalidades , Epiderme/fisiologia , Epiderme/fisiopatologia , Myxoma virus/crescimento & desenvolvimento , Myxoma virus/fisiologia , Myxoma virus/ultraestruturaRESUMO
Leprosy presents as a clinical spectrum that is precisely paralleled by a spectrum of immunological reactivity. The disease provides a useful and accessible model, in this case in the skin, in which to study the dynamics of cellular immune responses to an infectious pathogen, including the role of adhesion molecules in those responses. In lesions characterized by strong delayed-type hypersensitivity against Mycobacterium leprae (tuberculoid, reversal reaction, and Mitsuda reaction), the overlying epidermis exhibited pronounced keratinocyte intracellular adhesion molecule 1 (ICAM-1) expression and contained lymphocytes expressing the ICAM-1 ligand, LFA-1. Conversely, in lesions in which delayed-type hypersensitivity was lacking (lepromatous), keratinocyte ICAM-1 expression was low and LFA-1+ lymphocytes were rare. Expression of these adhesion molecules on the cells within the dermal granulomas was equivalent throughout the spectrum of leprosy. The percentage of lymphocytes in these granulomas containing mRNA coding for gamma interferon and tumor necrosis factor alpha, synergistic regulators of ICAM-1 expression, paralleled epidermal ICAM-1 expression. In lesions of erythema nodosum leprosum, a reactional state of lepromatous leprosy thought to be due to immune complex deposition, keratinocyte ICAM-1 expression and gamma interferon mRNA+ cells were both prominent. Antibodies to LFA-1 and ICAM-1 blocked the response of both alpha beta and gamma delta T-cell clones in vitro to mycobacteria. Overall, the expression of adhesion molecules by immunocompetent epidermal cells, as well as the cytokines which regulate such expression, correlates with the outcome of the host response to infection.