title: A peptide derived from the parasite receptor, complement C2 receptor inhibitor trispanning, suppresses immune complex-mediated inflammation in mice.
abstract: Complement C2 receptor inhibitor trispanning (CRIT) is a Schistosoma protein that binds the human complement protein, C2. We recently showed that peptides based on the ligand binding region of CRIT inhibit the classical pathway (CP) of complement activation in human serum, using hemolytic assays and so speculated that on the parasite surface CRIT has the function of evading human complement. We now show that in vitro the C2-binding 11-aa C terminus of the first extracellular domain of CRIT, a 1.3-kDa peptide termed CRIT-H17, inhibits CP activation in a species-specific manner, inhibiting mouse and rat complement but not that from guinea pig. Hitherto, the ability of CRIT to regulate complement in vivo has not been assessed. In this study we show that by inhibiting the CP, CRIT-H17 is able to reduce immune complex-mediated inflammation (dermal reversed passive Arthus reaction) in BALB/c mice. Upon intradermal injection of CRIT-H17, and similarly with recombinant soluble complement receptor type 1, there was a 41% reduction in edema and hemorrhage, a 72% reduction in neutrophil influx, and a reduced C3 deposition. Furthermore, when H17 was administered i.v. at a 1 mg/kg dose, inflammation was reduced by 31%. We propose that CRIT-H17 is a potential therapeutic agent against CP complement-mediated inflammatory tissue destruction.
authors.affiliation: Department of Research, University Hospital Basel, Basel, Switzerland.
authors.forename: Jameel M
authors.initials: JM
authors.lastname: Inal
authors.forename: Brigitte
authors.initials: B
authors.lastname: Schneider
authors.forename: Marta
authors.initials: M
authors.lastname: Armanini
authors.forename: Jürg A
authors.initials: JA
authors.lastname: Schifferli
mesh_terms: D000818:Animals; D000936:Antigen-Antibody Complex / Q000494:pharmacology*; D000947:Antigens, Helminth; D000953:Antigens, Protozoan / Q000008:administration & dosage / Q000494:pharmacology*; D001183:Arthus Reaction / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003176:Complement C3 / Q000378:metabolism; D003169:Complement Inactivator Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D004431:Ear, External; D005260:Female; D006168:Guinea Pigs; D015801:Helminth Proteins; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D007275:Injections, Intravenous; D015850:Interleukin-6 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D020556:Neutrophil Infiltration / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D015800:Protozoan Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011956:Receptors, Cell Surface / Q000008:administration & dosage; D017464:Receptors, Complement 3d / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012547:Schistosoma / Q000276:immunology; D012867:Skin / Q000276:immunology* / Q000473:pathology*; D013045:Species Specificity; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D000093242:Interleukin-6 Inhibitors
chemical_list: D000936:Antigen-Antibody Complex; D000947:Antigens, Helminth; D000953:Antigens, Protozoan; D003176:Complement C3; D003169:Complement Inactivator Proteins; D015801:Helminth Proteins; D007166:Immunosuppressive Agents; D015850:Interleukin-6; D010446:Peptide Fragments; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface; D017464:Receptors, Complement 3d; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C120046:TM3 protein, Schistosoma