DAMP production by XXXX islets under low @entity26 and nutrients in the presence or absence of an immunoisolating-capsule and necrostatin-1.

@entity1 @entity518 @entity26 @entity4100 @entity11620 @entity414
In between the period of transplantation and revascularization, pancreatic islets are exposed to low- @entity26 and low-nutrient conditions. In the present study we mimicked those conditions in vitro to study the involvement of different cell death processes, release of danger-associated molecular patterns (DAMP), and associated in vitro immune activation. Under low- @entity26 and low-nutrient conditions, apoptosis, autophagy and necroptosis occur in @entity1 islets. Necroptosis is responsible for DAMP-release such as dsDNA, @entity414 , and @entity518 . The sensors of the innate immune system able to recognize these DAMPs are mainly TLR, NOD receptors, and C-type lectins. By using cell-lines with a non-functional adaptor molecule @entity4100 , we were able to show that the islet-derived DAMPs signal mainly via TLR. Immunoisolation in immunoprotective membranes reduced DAMP release and immune activation via retention of the relative large DAMPs in the capsules. Another effective strategy was suppressing necroptosis using the inhibitor @entity11620 . Although the effect on cell-survival was minor, @entity11620 was able to reduce the release of @entity518 and its associated immune activation. Our data demonstrate that in the immediate post-transplant period islets release DAMPs that in vitro enhance responses of innate immune cells. DAMP release can be reduced in vitro by immunoisolation or intervention with @entity11620 .
