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BACKGROUND: A report of inflammatory damage when islets come into contact with allogeneic blood prompted us to confirm the finding. METHODS: Fresh handpicked human islets were incubated in blood group matched, nonsensitized allogeneic blood. Destruction was quantified by assaying the supernatants for proinsulin 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 C1q, 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 proinsulin 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 platelet aggregation with Reopro (n = 3), separately or together (n = 3), did not make a substantial improvement in the destruction in terms of histology or proinsulin release. Immunohistochemical staining (n = 4) revealed C1q, 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 human 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.

Original publication

DOI

10.1097/01.TP.0000064517.98252.00

Type

Journal article

Journal

Transplantation

Publication Date

27/04/2003

Volume

75

Pages

1317 - 1322

Keywords

Antibodies, Monoclonal, Anticoagulants, Blood Cell Count, Blood Coagulation, Blood Physiological Phenomena, Complement System Proteins, Heparin, Histocompatibility, Humans, Immunoglobulin Fab Fragments, Immunoglobulins, Immunohistochemistry, In Vitro Techniques, Islets of Langerhans, Proinsulin, Thrombelastography