Sephadex® induced granulomatous reaction in rats

Production of Granulomatous Inflammation in Lungs of Rat Pups and Adults by Sephadex Beads

“…Mononuclear cells were the primary cells found in the lesion, but eosinophils and neutrophils also accumulated appreciably in the lesions and their surroundings. These results are consistent with previous reports (7,10). Examination of the BALF also revealed significant increased counts of eosinophils …”

“…In rat and guinea pig models, Sephadex beads administered intravenously or intratracheally can cause granulomatous lesions with considerable accumulations of eosinophils and neu-trophils in the lungs (7)(8)(9)(10). When these particles initiated emboli in the pulmonary microvasculature, mononuclear cells, eosinophils, and neutrophils accumulated in the area and a granuloma was formed around the particle.…”

“…When these particles initiated emboli in the pulmonary microvasculature, mononuclear cells, eosinophils, and neutrophils accumulated in the area and a granuloma was formed around the particle. The granuloma gradually expanded, and inflammatory cells infiltrated the adjoining pulmonary alveoli, respiratory tract, and blood vessels (7,8,10). In contrast, only a limited mononuclear infiltrate was found in the Sephadex-treated lungs of a mouse model (3,6).…”

Inhibition of Pulmonary Eosinophilia Does Not Necessarily Prevent the Airway Hyperresponsiveness Induced by Sephadex Beads

“…In our preliminary examination, cyclosporin A which inhibits lymphocyte function could not inhibit Sephadex-induced AHR (data not shown). Previous studies by others [8, 9, 17] have also shown that the macrophage is a major cell component of the inflammatory response in noninbred rats injected with Sephadex beads. As the mechanism of attraction of macrophages, the involvement of macrophage chemoattractant protein I (MCP1) released by smooth muscle cells [18] should be considered.…”

“…We found that the structure of small arteries clogged with Sephadex beads was damaged. The damaged cells of the arteries released MCP1 and could be a target for the attracted macrophages with their proteolytic activity [17]. Macrophages are capable of elaborating a number of eosinophil chemoattractants such as tumor necrosis factor, eosinophil-activating factor, granulocyte-macrophage colony-stimulating factor and others [20].…”