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.
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References
- Ischaemia-reperfusion injury.Br J Surg. 1994; 81: 637-647
- Complement activation after oxidative stress: role of the lectin complement pathway.Am J Pathol. 2000; 156: 1549-1556
- Role for the alternative complement pathway in ischemia/reperfusion injury.Am J Pathol. 2003; 162: 449-455
- Mannose-binding lectin is a regulator of inflammation that accompanies myocardial ischemia and reperfusion injury.J Immunol. 2005; 175: 541-546
- Reperfusion injury of ischemic skeletal muscle is mediated by natural antibody and complement.J Exp Med. 1996; 183: 2343-2348
- Molecular mechanisms of complement activation during ischaemia and reperfusion.in: Vincent J.L. Yearbook of intensive care and emergency medicine. Springer, Berlin2002
- The major acute phase reactants: C-reactive protein, serum amyloid P component and serum amyloid A protein.Immunol Today. 1994; 15: 81-88
- Isolation and characterization of C-reactive protein and serum amyloid P component in the rat.Immunology. 1982; 45: 55-70
- Protection from Streptococcus pneumoniae infection by C-reactive protein and natural antibody requires complement but not Fc gamma receptors.J Immunol. 2002; 168: 6375-6381
- Specificity of C-reactive protein for choline phosphate residues of pneumococcal C-polysaccharide.Proc Soc Exp Biol Med. 1971; 136: 612-614
- C-reactive protein binds to both oxidized LDL and apoptotic cells through recognition of a common ligand: phosphorylcholine of oxidized phospholipids.Proc Natl Acad Sci U S A. 2002; 99: 13043-13048
- A role for secretory phospholipase A2 and C-reactive protein in the removal of injured cells.Immunol Today. 1997; 18: 111-115
- Isoelectric focus analysis of rat anti-phosphocholine antibodies.Biochemistry. 1977; 16: 5303-5308
- Levels of natural IgM antibodies against phosphorylcholine in healthy individuals and in patients undergoing isolated limb perfusion.J Immunol Methods. 2004; 293: 1-11
- I-PLA(2) activation during apoptosis promotes the exposure of membrane lysophosphatidylcholine leading to binding by natural immunoglobulin M antibodies and complement activation.J Exp Med. 2002; 196: 655-665
- CRP-mediated activation of complement in vivo: assessment by measuring circulating complement-C-reactive protein complexes.J Immunol. 1996; 157: 473-479
- Rat C-reactive protein activates the autologous complement system.Immunology. 2003; 109: 564-571
- E.J Clin Pathol. 2005; 58: 382-388
- C-reactive protein and complement are important mediators of tissue damage in acute myocardial infarction.J Exp Med. 1999; 190: 1733-1740
- Acute mesenteric ischemia: the challenge of gastroenterology.Surg Today. 2005; 35: 185-195
- The role of the complement system in ischemia-reperfusion injury.Shock. 2004; 21: 401-409
- Inhibition of complement C5 reduces local and remote organ injury after intestinal ischemia/reperfusion in the rat.Gastroenterology. 2001; 120: 126-133
- Murine model of gastrointestinal ischemia associated with complement-dependent injury.J Appl Physiol. 2002; 93: 338-345
- Soluble complement receptor type 1 ameliorates the local and remote organ injury after intestinal ischemia-reperfusion in the rat.J Immunol. 1992; 149: 1723-1728
- Antiinflammatory effects of soluble complement receptor type 1 promote rapid recovery of ischemia/reperfusion injury in rat small intestine.Clin Immunol. 1999; 90: 266-275
- Biological effects of C1 inhibitor.Drug News Perspect. 2004; 17: 439-446
- Human C1 esterase inhibitor attenuates murine mesenteric ischemia/reperfusion induced local organ injury.J Surg Res. 2003; 115: 247-256
- Local intravascular coagulation and fibrin deposition on intestinal ischemia-reperfusion in rats.Surgery. 2003; 133: 411-419
- The sequence of development of intestinal tissue injury after strangulation ischemia and reperfusion.Surgery. 1990; 107: 574-580
- Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity.Gastroenterology. 1984; 87: 1344-1350
- The potentiation of human C1-inhibitor by dextran sulphate is transient in vivo: studies in a rat model.Int Immunopharmacol. 2001; 1: 1583-1595
- Clearance of human native, proteinase-complexed, and proteolytically inactivated C1-inhibitor in rats.Blood. 1993; 81: 56-61
- Decreased smooth muscle cell/extracellular matrix ratio of media of femoral artery in patients with atherosclerosis and hyperhomocysteinemia.Arterioscler Thromb Vasc Biol. 2001; 21: 573-577
- The role of complement and natural antibody in intestinal ischemia-reperfusion injury.Int J Immunopathol Pharmacol. 2003; 16: 1-8
- Mice deficient in complement receptors 1 and 2 lack a tissue injury-inducing subset of the natural antibody repertoire.J Immunol. 2002; 169: 2126-2133
- Intestinal reperfusion injury is mediated by IgM and complement.J Appl Physiol. 1999; 86: 938-942
- Gastrointestinal ischemia-reperfusion injury is lectin complement pathway dependent without involving C1q.J Immunol. 2005; 174: 6373-6380
- Human serum IgM glycosylation: identification of glycoforms that can bind to mannan-binding lectin.J Biol Chem. 2005; 280: 29080-29087
- Activation of the lectin pathway by natural IgM in a model of ischemia/reperfusion injury.J Immunol. 2006; 177: 4727-4734
- Natural antibodies and the autoimmunity of atherosclerosis.Springer Semin Immunopathol. 2005; 26: 385-404
- Identification of a specific self-reactive IgM antibody that initiates intestinal ischemia/reperfusion injury.Proc Natl Acad Sci U S A. 2004; 101: 3886-3891
- Identification of the target self-antigens in reperfusion injury.J Exp Med. 2006; 203: 141-152
- IgM binding to injured tissue precedes complement activation during skeletal muscle ischemia-reperfusion.J Surg Res. 2004; 122: 29-35
- Complement regulatory protein C1 inhibitor binds to selectins and interferes with endothelial-leukocyte adhesion.J Immunol. 2003; 171: 4786-4791
- The differing roles of the classical and mannose-binding lectin complement pathways in the events following skeletal muscle ischemia-reperfusion.J Immunol. 2006; 177: 8080-8085
- Effect of supraphysiologic levels of C1-inhibitor on the classical, lectin and alternative pathways of complement.Mol Immunol. 2007; 44: 1819-1826
Article info
Publication history
Accepted:
May 11,
2007
Identification
Copyright
© 2007 Mosby, Inc. Published by Elsevier Inc. All rights reserved.