Adult porcine islets produce MCP-1 and recruit human monocytes in vitro

: Type 1 diabetes can be cured by transplantation of isolated pancreatic islets. Because of the shortage of human donor tissue, adult porcine islets (APIs) constitute a possible alternative tissue source. Upon intraportal injection, islets are subjected to an instant blood‐mediated inflammatory reaction (IBMIR) leading to blood clotting, leukocyte islet‐infiltration, islet damage and insulin release. Xenogeneic islets surviving IBMIR are rejected in a cellular process involving CD4+ T lymphocytes and macrophages. We have investigated whether APIs themselves produce and secrete chemokines and/or inflammatory cytokines that may contribute to IBMIR and/or cell‐mediated rejection. APIs, cultured for 1, 4, 8 and 11 days post‐isolation, expressed mRNA for monocyte chemoattractant protein‐1 (MCP‐1), IL‐1β and TNF‐α. API culture supernatants induced migration of human monocytes, which was significantly blocked by an anti‐human MCP‐1 antibody (Ab). Immunohistochemistry revealed MCP‐1 in the cytoplasm of α‐ and β‐cells in isolated islets and in islets in situ. However, APIs or their supernatants were not able to activate human aortic endothelial cells (HAECs) in vitro, and neither IL‐1β nor TNF‐α were detected by enzyme‐linked immunosorbent assay (ELISA) in API culture supernatants. Both recombinant porcine IL‐1β and TNF‐α were able to activate human endothelial cells (ECs) inducing CD62E and CD106 expression as analyzed by flow cytometry. In conclusion, MCP‐1 secreted by APIs may contribute to both IBMIR and rejection by attracting monocytes into the islet; monocytes which upon transformation into macrophages will potentiate antigen presentation and execute islet rejection.