title: C-reactive protein and natural IgM antibodies are activators of complement in a rat model of intestinal ischemia and reperfusion.
abstract: BACKGROUND
  The role of C-reactive protein (CRP), natural immunoglobulin M (IgM), and natural IgM against phosphorylcholine (anti-Pc IgM) was investigated in relation with complement activation in a rat model of intestinal ischemia and reperfusion (II/R). The effect of C1-esterase inhibitor (C1-Inh) on this complement activation along with other inflammatory mediators was also studied.
  
  
  METHODS
  Rats were subjected to 1 h of superior mesenteric artery occlusion and 3 h of reperfusion. Intravenous administration of vehicle (human albumin) or C1-Inh (200 U/kg) was performed before (n = 8) or after ischemia (n = 8). II/R increased levels of C4b/c, CRP, IgM, anti-Pc IgM, and myeloperoxidase activity in the intestinal homogenates and induced vascular leakage.
  
  
  RESULTS
  A good correlation was observed in the intestinal homogenates between C4b/c and CRP levels. Clear depositions of C3, CRP, and IgM in intestinal tissue were demonstrated after II/R, and a strong correlation of both CRP and IgM with complement was observed. C1-Inh administered before ischemia reduced the complement activation response after II/R, as reflected by decreased levels of C4b/c in conjunction with reduced anti-Pc IgM in the intestinal homogenates. C1-Inh also decreased leakage of albumin when administered before ischemia. C1-Inh after ischemia reduced C4b/c levels and myeloperoxidase activity in the homogenates.
  
  
  CONCLUSIONS
  CRP and IgM depositions correlated well with local complement activation, which suggests a role of these molecules in complement activation. Furthermore, C1-Inh inhibited potentially II/R injury either administered before or after ischemia, by attenuating complement activation induced by CRP and/or natural IgM antibodies.
authors.affiliation: Department of Immunopathology, Sanquin Research, Plesmalaan 125, Amsterdam, The Netherlands. niubel@hotmail.com
authors.forename: Niubel Diaz
authors.initials: ND
authors.lastname: Padilla
authors.forename: Arlène K
authors.initials: AK
authors.lastname: van Vliet
authors.forename: Ivo G
authors.initials: IG
authors.lastname: Schoots
authors.forename: Mercedes
authors.initials: M
authors.lastname: Valls Seron
authors.forename: M Adrie
authors.initials: MA
authors.lastname: Maas
authors.forename: Esther E Posno
authors.initials: EE
authors.lastname: Peltenburg
authors.forename: Annebeth
authors.initials: A
authors.lastname: de Vries
authors.forename: Hans W M
authors.initials: HW
authors.lastname: Niessen
authors.forename: C Erik
authors.initials: CE
authors.lastname: Hack
authors.forename: Thomas M
authors.initials: TM
authors.lastname: van Gulik
mesh_terms: D000818:Animals; D002097:C-Reactive Protein / Q000276:immunology* / Q000378:metabolism; D002199:Capillary Permeability / Q000276:immunology; D003167:Complement Activation; D003176:Complement C3 / Q000276:immunology / Q000378:metabolism; D015935:Complement C4b / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D007075:Immunoglobulin M / Q000276:immunology* / Q000378:metabolism; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000276:immunology* / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000473:pathology; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D010767:Phosphorylcholine / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000276:immunology* / Q000473:pathology
chemical_list: D003176:Complement C3; D007075:Immunoglobulin M; D010446:Peptide Fragments; C033860:complement C4c; D010767:Phosphorylcholine; D015935:Complement C4b; D002097:C-Reactive Protein