Arp2/3 Complex Is Required for Macrophage Integrin Functions but Is Dispensable for FcR Phagocytosis and In Vivo Motility

The Arp2/3 complex nucleates branched actin, forming networks involved in lamellipodial protrusion, phagocytosis, and cell adhesion. We derived primary bone marrow macrophages lacking Arp2/3 complex (Arpc2^−/−) and directly tested its role in macrophage functions. Despite protrusion and actin assembly defects, Arpc2^−/− macrophages competently phagocytose via FcR and chemotax toward CSF and CX3CL1. However, CR3 phagocytosis and fibronectin haptotaxis, both integrin-dependent processes, are disrupted. Integrin-responsive actin assembly and αM/β2 integrin localization are compromised in Arpc2^−/− cells. Using an in vivo system to observe endogenous monocytes migrating toward full-thickness ear wounds we found that Arpc2^−/− monocytes maintain cell speeds and directionality similar to control. Our work reveals that the Arp2/3 complex is not a general requirement for phagocytosis or chemotaxis but is a critical driver of integrin-dependent processes. We demonstrate further that cells lacking Arp2/3 complex function in vivo remain capable of executing important physiological responses that require rapid directional motility. Using a combination of cell culture-based and in vivo mouse experiments, Rotty et al. demonstrate that the actin-nucleating Arp2/3 complex is not absolutely required for macrophage FcR phagocytosis, chemotaxis, or in vivo monocyte directional motility. Rather, the complex has a critical role in regulating integrin-dependent macrophage processes.