A Precise Analysis of C5a Inhibitory Peptide on Inflammatory Mediators Induced After Islet Transplantation

Abstract Objective We recently reported that C5a inhibitory peptide (C5aIP) prevents the instant blood-mediated inflammatory reaction by attenuating cross talk between complement and coagulation cascades. C5aIP has also been shown to possess a broad range of anti-inflammatory effects. Due to methodo...

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Bibliographic Details
Published in:Transplantation proceedings 2011-11, Vol.43 (9), p.3235-3238
Main Authors: Nakanishi, W, Masafumi, G, Inagaki, A, Sekiguchi, S, Fujimori, K, Okada, N, Okada, H, Satomi, S
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Blood Coagulation
CD11b Antigen - biosynthesis
Complement C5a - antagonists & inhibitors
Complement System Proteins
Cytokines - metabolism
Flow Cytometry
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Gene Expression Regulation
Inflammation
Inflammation Mediators - pharmacology
Interferon-gamma - metabolism
Islets of Langerhans - cytology
Islets of Langerhans Transplantation - methods
Medical sciences
Mice
Rats
Serine Endopeptidases - pharmacology
Surgery
Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases
Time Factors
Tissue, organ and graft immunology
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Summary:Abstract Objective We recently reported that C5a inhibitory peptide (C5aIP) prevents the instant blood-mediated inflammatory reaction by attenuating cross talk between complement and coagulation cascades. C5aIP has also been shown to possess a broad range of anti-inflammatory effects. Due to methodological limitations, it is difficult to perform detailed analyses on wide range of inflammatory mediators in rat model. Therefore, we examined whether C5aIP suppressed various inflammatory cytokines induced after islet transplantation using a mouse model. Methods Six islet equivalents per gram of syngeneic mouse islet grafts were transplanted intraportally into two groups of streptozotocin-induced diabetic mice: control group ( n = 8) and C5aIP group ( n = 6). The C5aIP group was treated with a bolus of 4 mg/kg just after islet infusion and a continuous infusion of 0.4 mg/kg/h, whereas the control group was injected with equivalent amounts of saline. Serum samples were collected at 0, 6, and 24 hours after transplantation. We analyzed 23 types of cytokines: interleukins-1a, -1b, -3, -4, -5, -6, -9, -10, -12, -13, and -17; eotaxin; G-CSF; GM-CSF; interferon (INF) gamma; KC; MCP-1; MIP-1 and -1b, RANTES and tumor necrosis factor-alpha. Leukocytes in the recipient liver were isolated at 6 hours after transplantation to examine IFN gamma production by fluorescence activated cell sorting (FACS). Results No significant difference was detected in terms of the major inflammatory cytokines between the two groups. INF gamma production on CD11b+ Gr-1+ cells in the liver was not significantly inhibited by C5aIP (control 30.0% vs C5aIP 24.1%). Conclusions These data suggested that beneficial effects of C5aIP on islet engraftment are mainly due to blockade of cross talk between complement and coagulation cascades, rather than the suppression of inflammatory mediators.
ISSN:0041-1345
1873-2623
DOI:10.1016/j.transproceed.2011.10.026