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: 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
• Journal: Surgery (Surgery) Vol. 142 Issue 5 Pg. 722-33 (Nov 2007) ISSN: 0039-6060 [Print] United States
• PMID: 17981193 (Publication Type: Journal Article)

Chemical References

• Complement C3
• Immunoglobulin M
• Peptide Fragments
• complement C4c
• Phosphorylcholine
• Complement C4b
• C-Reactive Protein

Topics

• Animals
• C-Reactive Protein (immunology, metabolism)
• Capillary Permeability (immunology)
• Complement Activation
• Complement C3 (immunology, metabolism)
• Complement C4b (immunology, metabolism)
• Disease Models, Animal
• Immunoglobulin M (immunology, metabolism)
• Immunohistochemistry
• Intestinal Mucosa (metabolism)
• Intestines (immunology, pathology)
• Male
• Neutrophils (pathology)
• Peptide Fragments (immunology, metabolism)
• Phosphorylcholine (immunology)
• Rats
• Rats, Wistar
• Reperfusion Injury (immunology, pathology)