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The Arp2\/3 complex has been implicated in iC3b-mediated macrophage phagocytosis, but it is unclear whether it is similarly required in microglia in the CNS. We examined the question of CR3-dependent clearance of iC3b in microglia using a combination of in vitro and in situ physical confinement studies. Arp2\/3 inhibition decreased iC3b phagocytosis and cell motility in vitro. Furthermore, microglia-like cells remove immobilized iC3b from the substrate in an Arp2\/3-dependent fashion, in a process reminiscent of trogocytic synaptic pruning. We also used a novel approach to immobilize an iC3b gradient onto a substrate and demonstrate Arp2\/3-dependent haptotactic migration toward increasing iC3b concentrations. While Arp2\/3-deficient microglia robustly respond to ATP via chemotaxis within mouse hippocampal slices, they demonstrate a persistent inability to stably interact with iC3b-coated beads. 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