Adverse outcome of XXXX islet-allogeneic blood interaction.

@entity1 @entity2690 @entity1423 @entity6300
BACKGROUND: A report of inflammatory damage when islets come into contact with allogeneic blood prompted us to confirm the finding. METHODS: Fresh handpicked @entity1 islets were incubated in blood group matched, nonsensitized allogeneic blood. Destruction was quantified by assaying the supernatants for @entity2690 release and by blood clot histology. The effect on global hemostasis was assessed by thromboelastography (TEG), and heparin-bonded tubing was used to assess the effect on blood cellular counts. In separate experiments, islets were incubated in allogeneic blood with heparin or Reopro (monoclonal anti-GpIIbIIIa). Islets were also incubated in serum, and cryosections were stained for @entity6300 , C4, C3, C5b-9, immunoglobulin (Ig)M, and IgG binding using immunohistochemistry. RESULTS: Histologic assessment showed severe destruction in 37% of islets in contact with allogeneic blood versus none in controls and a sevenfold increase in @entity2690 release from controls (n = 6)(P < 0.005). TEG (n = 11) showed accelerated coagulation in the presence of islets (P < 0.001). Analysis of blood cellular counts (n = 3) showed consumption of platelets, neutrophils, and monocytes in the presence of islets (P < 0.001). Inhibition of coagulation with heparin (n = 3) or inhibition of @entity1423 with Reopro (n = 3), separately or together (n = 3), did not make a substantial improvement in the destruction in terms of histology or @entity2690 release. Immunohistochemical staining (n = 4) revealed @entity6300 , C4, C3, and C5b-9 deposition along with IgG binding. IgM binding was weak if anything. CONCLUSION: This study confirms and extends the finding that @entity1 islet-allogeneic blood interaction results in significant destruction of islet tissue with activation of the coagulation cascade and platelet, neutrophil, and monocyte consumption. There was evidence for activation of complement by the classical pathway along with IgG binding.
