Elimination of the fibrinogen integrin α_Mβ₂-binding motif negates the requirement of plasminogen for macrophage migration through fibrin matrices. Neither RAW 264.7 cells (A) nor BMDMs (B) migrate through wild-type fibrinogen in the absence of plasminogen (Column 1) that is restored in the presence of plasminogen (Column 2). However, neither cell type requires plasminogen to migrate through fibrin matrices if the integrin α_Mβ₂-binding site is abrogated (Column 3). A further increase in migration, even in the absence of the α_Mβ₂-binding motif, is seen with the addition of plasminogen (Column 4). (C-J) Representative transwell membranes from wild-type fibrinogen without (C-D) or with (E-F) plasminogen show migration only in the presence of plasminogen; low power imaging (10×) with higher power magnification (as noted by square outline). Panels D, F, H, and J exhibit higher power imaging of the transwell membrane. Macrophages readily migrated without (G-H) or with (I-J) plasminogen if fibrin was formed from Fibγ^390-396A plasma. Scale bars in panels C, E, G, and I indicate 1 mm. Scale bars in panels D, F, H, and J indicate 100 µm. N.S., not significant.