Fig 1: Graphical summary of hypothesis. The data presented here support the hypothesis that upon activation with tumour necrosis factor (TNF) (and potentially other inflammatory mediators), neutrophils rapidly release microvesicles into their local environment. Subsets of these vesicles express the pro-resolving protein annexin A1 (AnxA1) and/or phosphatidylserine (PtdSer) exposed on their outer membrane leaflet. The vesicles attenuate macrophage activation in response to lipopolysaccharide (LPS) and interferon gamma (IFN-?), and influence their ability to activate other cell types, such as fibroblast-like synoviocytes in the rheumatoid synovium. Two mechanisms have been identified as responsible for these effects: AnxA1 activating FPR2 and inducing the release of transforming growth factor ß (TGFß), and PtdSer activating MerTK which blocks classical activation.