Attenuation of Cross-Talk Between the Complement and Coagulation Cascades by C5a Blockade Improves Early Outcomes After Intraportal Islet Transplantation

作者：Tokodai Kazuaki; Goto Masafumi^*; Inagaki Akiko; Nakanishi Wataru; Ogawa Norihiko; Satoh Kazushige; Kawagishi Naoki; Sekiguchi Satoshi; Nilsson Bo; Okada Noriko; Okada Hidechika; Satomi Susumu

来源：Transplantation, 2010, 90(12): 1358-1365.

DOI：10.1097/TP.0b013e3181ffb9f5

• Islets
• Transplantation
• Complement
• C5a
• Tissue factor

Background. Complement 5a factor (C5a) elicits a broad range of proinflammatory effects, including chemotaxis of inflammatory cells and cytokine release. C5a is also linked to the coagulant activity in autoimmune diseases. Therefore, C5a most likely plays a crucial role in the instant blood-mediated inflammatory reaction.
Methods. Intraportal transplantation of 2.5 islet equivalents/g of syngeneic rat islet grafts was performed in two groups of streptozotocin-induced diabetic rats: controls and C5a inhibitory peptide (C5aIP)-treated group.
Results. The thrombin-antithrombin complex was significantly suppressed in the C5aIP group (P = 0.003), and both the curative rate and the glucose tolerance were significantly improved in the C5aIP group (P < 0.05 and P < 0.005, respectively). Expression of tissue factor on granulocytes in recipient livers was up-regulated 1 h after islet infusion (P < 0.0001), which was significantly suppressed by C5aIP (P < 0.005). However, C5aIP was unable to regulate tissue factor expression on isolated islets. Furthermore, no differences were detected between the groups, regarding infiltration of CD11b-positive cells and deposition of C5b-9 on the islet grafts.
Conclusions. These data suggest that C5aIP attenuates cross-talk between the complement and coagulation cascades through suppressing up-regulation of tissue factor expression on leukocytes in recipient livers but not on islet grafts, a process leading to improvement in islet engraftment. Therefore, C5aIP in combination with conventional anticoagulants could be a strong candidate strategy to control the instant blood-mediated inflammatory reaction induced in clinical islet transplantation.

• 出版日期2010-12-27