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Background/Aims:   Healing of mesangioproliferative glomerulonephritis involves degradation of excess extracellular matrix, resolution of hypercellularity by apoptosis and phagocytosis of apoptotic cells. Integrin receptors participate in the regulation of phagocytosis. In mice deficient for alpha8 integrin ( Itga8 -/-) healing of glomerulonephritis is delayed. As  Itga8  is abundant in mesangial cells (MC) which are non-professional phagocytes, we hypothesized that  Itga8  facilitates phagocytosis of apoptotic cells and matrix components by MC.   Methods:   MC were isolated from wild type (WT) and  Itga8 -/- mice. Latex beads were coated with matrix components. Apoptosis was induced by cisplatin in macrophages and in DiI-stained MC. After coincubation of latex beads or apoptotic cells with MC, the phagocytosis rate was detected in WT and  Itga8 -/- MC via fluorescence microscopy and FACS analysis.   Results:    Itga8 -/- MC showed reduced phagocytosis of matrix-coated beads and apoptotic cells compared to WT MC. Reduction of stress fibers was observed in  Itga8 -/- compared to WT MC. Inhibition of cytoskeletal reorganization by inhibition of Rac1 or ROCK during phagocytosis significantly decreased the rate of phagocytosis by WT MC but not by  Itga8 -/- MC.   Conclusion:   The expression of  Itga8  facilitates phagocytosis in MC, likely mediated by  Itga8 -cytoskeleton interactions. An impairment of MC phagocytosis might thus contribute to a delayed glomerular regeneration in  Itga8 -/- mice.

Expression of the Alpha8 Integrin Chain Facilitates Phagocytosis by Renal Mesangial Cells