2 resultados para Chronicity
Resumo:
Neovascular retinal disease is a leading cause of blindness orchestrated by inflammatory responses. Although noninfectious uveoretinitis is mediated by CD4(+) T cells, in the persistent phase of disease, angiogenic responses are observed, along with degeneration of the retina. Full clinical manifestation relies on myeloid-derived cells, which are phenotypically distinct from, but potentially sharing common effector responses to age-related macular degeneration. To interrogate inflammation-mediated angiogenesis, we investigated experimental autoimmune uveoretinitis, an animal model for human uveitis. After the initial acute phase of severe inflammation, the retina sustains a persistent low-grade inflammation with tissue-infiltrating leukocytes for over 4 months. During this persistent phase, angiogenesis is observed as retinal neovascular membranes that arise from inflamed venules and postcapillary venules, increase in size as the disease progresses, and are associated with infiltrating arginase-1(+) macrophages. In the absence of thrombospondin-1, retinal neovascular membranes are markedly increased and are associated with arginase-1(-) CD68(+) macrophages, whereas deletion of the chemokine receptor CCR2 resulted in reduced retinal neovascular membranes in association with a predominant neutrophil infiltrate. CCR2 is important for macrophage recruitment to the retina in experimental autoimmune uveoretinitis and promotes chronicity in the form of a persistent angiogenesis response, which in turn is regulated by constitutive expression of angiogenic inhibitors like thrombospondin-1. This model offers a new platform to dissect the molecular and cellular pathology of inflammation-induced ocular angiogenesis.
Resumo:
In the summer of 1990 an epizootic infection caused by a morbillivirus (DMV) killed several thousand striped dolphins (Stenella coeruleoalba) in the Mediterranean Sea. In 1991 and 1992 the epizootic reached Italian and Greek waters. The infection by DMV in the acute period of the epizootic caused encephalitis, pneumonia and depletion of lymph nodes. After 1990, the systemic infection apparently disappeared from the Catalonian coast, giving way to cases of chronic infection of the CNS. Dolphins that died between 1991 and May 1994 were necropsied, and investigated for lesions due to DMV, and for the presence of morbillivirus antigen in tissues. Encephalitis occurred in 6 dolphins in which DMV antigen was demonstrated in the CNS and which were without lesions or antigen in other, non-nervous tissues. Inflammatory lesions, gliosis, and DMV antigen decreased in density and amount from cerebral grey matter, through the thalamic areas to the medulla oblongata. The cerebellum was usually spared. Lesions consisted of non-suppurative encephalitis, with diffuse gliosis and glial nodules and neuronophagia, and loss of neurons. Perivascular cuffing of lymphocytes and plasma cells was present in the cerebral cortex and the white matter beneath the cortex. Multinucleate syncytia were not detected in any of the dolphins. The haemagglutinin of DMV was detected mainly in neurons in the cerebral cortical areas. There was no clear relationship between the presence and amount of DMV antigen and the density or chronicity of lesions. Viral inclusions were seen in haematoxylin and eosin stained sections in 3/6 dolphins, principally in the nucleus and the cytoplasm of neurons. In the immunoperoxidase stained sections, dense granular deposits of chromogen, similar to viral inclusions, were evident in all 6 dolphins. The change in the distribution of lesions and of DMV antigen, from systemic to localized in the CNS, and the clustering of systemic DMV infections in the first four months of the epizootic, giving rise to sporadic occurrence of local CNS infection in the subsequent four years, as well as the chronic nature of the CNS lesions, which closely resembles subacute sclerosing panencephalitis, strongly support the existence of a chronic morbillivirus infection in the striped dolphin, as a delayed consequence of the 1990 epizootic.