Schematic representation of the proposed role of the Plg/Pla system in the resolution of inflammation. The results of previous studies and of the current study indicate that the Plg/Pla system contributes to the termination of the inflammatory process by regulating distinct steps of resolution.^{12,13,15,16,18-20,53,54}  It has been previously shown that Pla induces monocyte recruitment from the bloodstream to inflammatory sites,^12,13,15,16  a critical step in acute inflammation that enables further clearance of apoptotic neutrophils and orderly progression toward resolution (1). Our current data also suggest that Plg and Pla induce polarization of macrophages to M2, which are highly efferocytic, and Mres subtypes, which are known to express high levels of anti-inflammatory, antifibrotic, and antioxidant mediators (2).^9,22  Furthermore, we demonstrate that the Plg/Pla system promotes neutrophil apoptosis in the inflammatory milieu (3) and enhances the efferocytosis capacity of macrophages (4). The underlying mechanism is associated with increased AnxA1 expression and activity because the absence of AnxA1 prevents neutrophil apoptosis and efferocytosis promoted by Plg. This is supported by reports indicating that AnxA1 acts as a bridging molecule between phosphatidylserine (PS) on the dying cell and the phagocyte favoring efferocytosis.^37,38,67  Together, these steps may contribute to the reduced accumulation of neutrophils in the inflammatory site promoted by Plg/Pla in the pleurisy model. The proresolving effects summarized in this figure (1-4) were described for both active Pla and its zymogen, Plg. Arrows linking Plg to Pla indicate a requirement of Pla protease activity for the proresolving effect of Plg. Our findings and those of others suggest that the effects of Plg on resolution require its conversion to active Pla, as demonstrated for Plg-induced monocyte recruitment,^15,16  efferocytosis,^18-20  and Arg-1 stimulation on macrophages.