title: 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 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.
authors.affiliation: Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, Sendai, Japan. wataru.nakanishi@gmail.com
authors.forename: W
authors.initials: W
authors.lastname: Nakanishi
authors.forename: M
authors.initials: M
authors.lastname: Goto
authors.forename: G
authors.initials: G
authors.lastname: Masafumi
authors.forename: A
authors.initials: A
authors.lastname: Inagaki
authors.forename: S
authors.initials: S
authors.lastname: Sekiguchi
authors.forename: K
authors.initials: K
authors.lastname: Fujimori
authors.forename: N
authors.initials: N
authors.lastname: Okada
authors.forename: H
authors.initials: H
authors.lastname: Okada
authors.forename: S
authors.initials: S
authors.lastname: Satomi
mesh_terms: D000818:Animals; D001777:Blood Coagulation; D039481:CD11b Antigen / Q000096:biosynthesis; D015936:Complement C5a / Q000037:antagonists & inhibitors*; D003165:Complement System Proteins; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D007249:Inflammation; D018836:Inflammation Mediators / Q000494:pharmacology; D007371:Interferon-gamma / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D051379:Mice; D051381:Rats; D012697:Serine Endopeptidases / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D039481:CD11b Antigen; D016207:Cytokines; D018836:Inflammation Mediators; C041833:complement C5a-inhibitors; D015936:Complement C5a; D007371:Interferon-gamma; D003165:Complement System Proteins; D012697:Serine Endopeptidases