C-reactive protein and natural IgM antibodies are activators of complement in a rat model of intestinal ischemia and reperfusion

Niubel Diaz Padilla, Arlène K van Vliet, Ivo G Schoots, Mercedes Valls Seron, M Adrie Maas, Esther E Posno Peltenburg, Annebeth de Vries, Hans W M Niessen, C Erik Hack, Thomas M van Gulik

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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.

Original languageEnglish
Pages (from-to)722-33
Number of pages12
Issue number5
Publication statusPublished - Nov 2007


  • Animals
  • C-Reactive Protein
  • Capillary Permeability
  • Complement Activation
  • Complement C3
  • Complement C4b
  • Disease Models, Animal
  • Immunoglobulin M
  • Immunohistochemistry
  • Intestines
  • Journal Article
  • Male
  • Neutrophils
  • Peptide Fragments
  • Phosphorylcholine
  • Rats
  • Rats, Wistar
  • Reperfusion Injury

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