A novel mechanism for protecting the arthritic joint: microparticles deliver Annexin A1 into cartilage (146.8)

• DOI: 10.1096/fasebj.28.1_supplement.146.8
• Publication Date: 2021-06-16T09:58:03Z
• Authors: Sarah Headland; Lucy Norling; Hetal Patel; Jesmond Dalli; Stephen Kelly; Costantino Pitzalis; Francesco Dell'Accio; Mauro Perretti
• Keywords: Annexin A1; Annexin A5

Microparticles (MPs), subcellular vesicles released from most eukaryotic cells, play important roles in inflammation. We found abundant endogenous neutrophil MPs present rheumatoid arthritis (RA) synovial fluid compared to paired plasma analyses. These were highly enriched Annexin A1 (AnxA1), a potent anti‐inflammatory protein. Addition of vitro generated AnxA1 +ve IL‐1‐stimulated 3D chondrocyte cultures, rodent cartilage explants, or injected intra‐articularly model inflammatory arthritis, surprisingly, afforded protection arthritogenesis. This was evidenced by reduced matrix degradation and mediator production an increase matrix‐synthesis gene expression, effects mediated primarily its receptor FPR2/ALX. Current dogma dictates that is impenetrable avascular through which metabolites must diffuse; we the first evidence can access chondrocytes vivo . Adoptive transfer fluorescently labeled mouse neutrophils i.v. into mice at peak demonstrated presence within arthritic (wrists, digits), but not intact (femoral head) cartilage, naïve mice. With this data propose with could offer therapeutic possibilities situ patients. Grant Funding Source : Supported The Oliver Bird Rheumatism Programme, Nuffield Foundation; Wellcome Trust