| Mesothelial cell autoantibodies (MCAA) are a form of tissue-specific autoantibody found in populations exposed to Libby Amphibole asbestos. We demonstrate that MCAA target plasminogen at the mesothelial cell surface. Mesothelial cells have not been previously recorded as binding plasminogen, meaning the receptors for plasminogen have also not been reported. Flow cytometry and plasmin activity assays were used to determine the plasminogen receptors on the surface of mesothelial cells. Mesothelial cells were found to express four plasminogen receptors on their surface including: α-Enolase, Annexin A2, Plg-RKT, and Histone H2B. Additionally, we assessed the effect of citrullination on plasmin activity, since this post-translational modification is common in systemic autoimmune diseases. Citrullination inhibited the activation of plasminogen on mesothelial cells but increased binding of MCAA. Together, these data help us understand the PLG-MCAA-mesothelial cell binding mechanism, and takes us one step closer to the development of a therapeutic for Libby Amphibole associated pathologies. |