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Saori Yaguchi, Yoko Ogawa, Shigeto Shinmura, Kazuo Tsubota; Lacrimal Gland Inflammation And Fibrosis In Murine Model Of Ocular Graft Versus Host Disease. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3720.
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The lacrimal glands of patients with chronic graft versus host disease (cGVHD) following allogeneic hematopoietic stem cell transplantation (HSCT) show prominent fibrosis and infiltrate of inflammatory cells in the glandular interstitium. We examined the mechanism how the inflammatory cells and fibroblasts were involved in the inflammation and fibrosis using a murine model of ocular cGVHD.
We generated murine model of ocular cGVHD by previously reported methods (Zhang Y et al.J Immunol.2002). In this model, irradiated BALB/c mice transplanted with minor histocompatibility mismatched B10.D2 bone marrow and spleen cells develop lacrimal gland fibrosis within 3 weeks after bone marrow transplantation (BMT), and progress over months. Mice transplanted with syngeneic BALB/c bone marrow and spleen cells were used as control. Lacrimal gland specimens were obtained from GVHD and control mice 3 weeks after BMT. The sectioned tissue were examined under both light and transmission electron microscope. Immunohistochemistry was performed on sections of lacimal grands to study the expression of CD3, CD19, CD45, F4/80 and HSP47 on infiltrating cells. Fibroblasts from lacrimal grand of control and cGVHD mice were isolated. Cells at passage 3 were used for immunostaining for HSP47.
Light microscopy of the murine GVHD lacrimal gland showed infiltration of inflammatory cells around medium sized ducts and severely fibrotic interstitium that was more intense in the periductal areas. Electron microscopic analysis of the periductal areas of murine cGVHD lacrimal gland revealed the newly synthesized collagen fibrils in the extra cellular matrix and the stromal fibroblasts were attached to other inflammatory cells such as macrophages and lymphocytes. Immunohistochemical analysis revealed infiltrating cells in the murine cGVHD lacrimal gland expressing the hematopoietic marker CD45, macrophage marker F4/80 and a fibroblast marker HSP47. Fibroblasts from lacrimal grand of cGVHD mice were relatively small, spindle shaped and the expression of HSP47 was elevated, which demonstrate high activity of collagen secretion.
These findings indicate that infiltration of inflammatory cells and fibroblasts in the periductal areas was involved in the pathogenic process of inflammation and fibrosis in murine cGVHD lacrimal glands.
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