Complement receptor-3-dependent removal of desialylated neurites. A, B, Cultured neurons were untreated or sialidase treated and then cocultured for 24 h with microglia. Cells were immunostained with antibodies directed against βIII-tubulin and Iba-1. Sialidase-treated neurons displayed shorter and discontinuous neurites compared with untreated neurons. Scalebar, 20 μm, n = 3. C, D, Normal or desialylated neurons (+ sialidase) were cocultured for 24 h with microglia (+ microglia) and neurite length of neurons was determined. C, Addition of microglia reduced the length of desialylated neurites (***p = 0.001 vs untreated, *p = 0.044 vs treated, **p = 0.009 vs + microglia). D, Reduction in desialylated neurite length by microglia was reversed after blockade of CR3 with a CD11b-specific antibody (+ anti-CD11b, *p = 0.016) compared with an isotype control (+ isotype Ab). * vs + sialidase + microglia and vs + sialidase + microglia + isotype Ab, n = 3.