Abstract 15333: An Intermediary for Sirpα/Skap2-dependent Integrin-Stimulated Cytoskeletal Rearrangement in Macrophages, and the Implications for Atherosclerosis

Background: Integrins mediate macrophage behaviors that are critical for atherogenesis. The macrophage membrane protein Sirpα cooperates with the adaptor protein Skap2 to control integrin-induced actin reorganization and migration. We hypothesized that CD47 interacts with these proteins to control actin polymerization and that, through their roles in macrophage function, these signaling elements modulate atherosclerosis. Results: Because Sirpα cooperates with Skap2 in an integrin-dependent manner, and because Sirpα is a known receptor for CD47, we tested integrin-induced actin polymerization in CD47-/- bone marrow-derived macrophages (BMMs). Similar to Skap2- and Sirpα-deficient cells, CD47-/- BMMs have impaired local integrin-induced actin polymerization compared to wild-type BMMs (1.1 ± 0.4 units vs. 7.9 ± 1.7 units, n = 20, p < 10-4). Furthermore, we find enhanced recruitment of CD47 to sites of antibody-mediated integrin ligation (3.1 ± 0.7 units vs. 1.0 ± 0.4 units for control antibody, n = 20, p < 5...