Selective inhibition of the alternative complement pathway by sCR1[desLHR-a]protects the rabbit isolated heart from human complement-mediated damage

doi:10.1016/0162-3109(96)00105-1

Immunopharmacology

Volume 34, Issues 2–3, September 1996, Pages 79-88

Immunopharmacology

https://doi.org/10.1016/0162-3109(96)00105-1 Get rights and content

Abstract

Evidence is presented that treatment with a selective inhibitor of the alternative complement pathway, sCR1[desLHR-A], protects the ex vivo perfused rabbit heart from human complement-mediated injury. Hearts from male New Zealand white rabbits were perfused in the Langendorff mode. After equilibration, normal human plasma was added to the perfusate as a source of complement. Concomitant with the addition of human plasma, vehicle (n = 13), soluble complement receptor type 1 (sCRI) (n = 10), or sCRI[desLHR-A], a truncated version of sCR1 that lacks the C4b binding region (n = 10) was included in the perfusate. Hemodynamic variables were obtained for all groups before (baseline) and after the addition of human plasma. Compared to vehicle-treated hearts, variables recorded during perfusion with human plasma including coronary perfusion pressure, left ventricular developed pressure, and left ventricular end diastolic pressure, along with a reduction of creatine kinase efflux, were improved in hearts perfused with either complement inhibitor. In addition, in vitro hemolysis assays were utilized to discriminate between the classical and alternative pathways. The addition of sCRI to human serum prevented both the classical and alternative pathway-mediated hemolysis while sCR1[desLHR-A]prevented only the alternative pathway-mediated lysis. This study indicates that deletion of the C4b-binding site from sCR 1 results in a new pharmacological moiety, sCRI[desLHR-A], that primarily inhibits the alternative pathway of human complement.

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Selective inhibition of the alternative complement pathway by sCR1[desLHR-a]protects the rabbit isolated heart from human complement-mediated damage

Abstract

J Thorac Cardiovasc Surg

J Biol Chem

Lancet

Complement in organ transplantation. Contributions to inflammation, injury, and rejection

Transplantation

Cardiac transplantation: immune mechanisms and alloantigens involved in graft rejection

Crit Rev Immunol

Complement and neutrophil activation in the pathogenesis of ischemic myocardial injury

Circulation

Regulation of the amplification C3 convertase of human complement by an inhibitory protein isolated from human erythrocyte membrane

Soluble complement receptor type 1 ameliorates the local and remote organ injury after intestinal ischemia-reperfusion in the rat

J Immunol

The phlogistic role of C3 leukotactic fragments in myocardial infarcts of rats

J Exp Med

Complement activation and inhibition in myocardial ischemia and reperfusion injury

Annu Rev Pharmacol Toxicol

Effects of complement activation in the isolated heart

Soluble complement receptor type I prevents human complementmediated damage of the rabbit isolated heart

J Immunol

Complement receptor is an inhibitor of the complement cascade

J Exp Med

The complement system in myocardial ischaemia/reperfusion injury

Cardiovasc Res

Identification of distinct C3b and C4b recognition sites in the human C3b/C4b receptor (CR1, CD35) by deletion mutagenesis

J Exp Med