Chemotactic Activity of Culture Supernatants of Free and Encapsulated Pancreatic Rat Islets Towards Peritoneal Macrophages

Longterm efficiency of encapsulated pancreatic islet transplantation is limited by macrophagic reaction at the surface of biocompatible membrane. The aim of this work was to investigate the influence of soluble factors released by free and encapsulated islets on macrophage chemotaxis. The culture mediums conditioned for 6 days by free and encapsulated rat islets were incubated with peritoneal murine, rat allo and syngenic macrophages to study their migration. Culture supernatants of rat fibroblasts and acinar cells, glucose-stimulated free rat islets and supernatants of free rat islets treated by heat and proteinase K were also tested for their chemotactic activity. Islets encapsulation decreased the chemotactic activity of culture medium conditioned for 6 days by free rat islets on murine (1.66 ± 0.20 vs. 3.10 ± 0.23; p < 0.001, n = 5) and rat allogenic macrophages (1.63 ± 0.21 vs. 4.70 ± 0.36; p < 0.001, n = 9). There was no migration of rat macrophages towards syngenic islets. Fibroblasts exhibited a very strong chemotactic effect as compared to acinar cells. Insulin was not involved in macrophage migration. Proteinase K treatment of culture supernatant of free rat islets totally inhibited the chemotactic activity. After heating at 56°C and 100°C, this activity was reduced to 41 ± 7% and 32 ± 5% of the initial activity, respectively. In conclusion, pancreatic islet stimulated macrophage migration by release of immunological specific proteins partly retained by macroencapsulation.

Key words

Chemotactic Factor - Bioartificial Pancreas - Artificial Membrane - Cell Migration - Leucocyte