Biomedical subjects

M Chrupcala

Publications and source records attributed to M Chrupcala.

3 recordsLinked to original sources

PubMed1998

[Significance of the complement system for xenotransplantation: strategies for therapeutic intervention].

Hyperacute graft rejection triggered by the activation of the recipient's complement system represents the major obstacle to successful xenotransplantation. After the binding of preformed antibodies to vascular glycoproteins complement-induced activation and injury of endothelial cells with subsequent thrombosis leads to rapid destruction of foreign tissues. Inhibition of complement activation is therefore considered as a prerequisite for xenograft survival. Recent animal and cell culture experiments suggest that support of the physiological regulation of the complement system appears to be most promising. Besides the application of soluble complement inhibitors (e.g. soluble complement receptor 1, sCR1; C1 inhibitor) the genetic transfer of human membrane-bound complement regulatory proteins (e.g. DAF, CD59) offers new chances to protect the xenograft against the cytolytic complement attack. Results from the authors' experiments shall be included in a short overview to the issue.

Animals↗

PubMed1996

[Effect of complement modulation with the soluble complement receptor sCR1 on survival and function of kidney xenotransplant. An experimental study with a new guinea pig to rate transplant model].

In this study a modified experimental kidney xenograft model was developed, which reproduced, in a reliable way, the course of hyperacute rejection. In this model guinea-pig kidneys were transplanted to rats using end-to-side anastomoses with recipient aorta and vena cava, respectively, and ureter drainage for diuresis monitoring. The aim of this study was to investigate the protective effects of complement modulation by soluble complement receptor 1 (sCR1) on the xenografts. Twenty-four xenotransplantations were performed and recipients randomized for treatment either by 3 ml saline or 50 mg/kg sCR1 as a 3-ml bolus. It was found that sCR1 was highly efficient in delaying hyperacute rejection from 10.5 +/- 2.1 min in the control group to at least 2 h in the therapy group and in prolongation of graft function. The complement activity was significantly reduced in the sCR1-treated rats, even at the time of rejection, as a result of complement modulation in this group of xenograft recipients. Xenografts from saline-treated animals showed necroses, interstitial haemorrhages and platelet aggregates occluding the vessels as soon as 10 min after the reperfusion started. No such changes could be seen even after 120 min in the xenografted kidneys of sCR1-treated rats. Also C3 deposits in the glomeruli and interstitium were markedly reduced.

Animals↗

PubMed1994

Prolongation of discordant renal xenograft survival by depletion of complement. Comparative effects of systemically administered cobra venom factor and soluble complement receptor type 1 in a guinea-pig to rat model.

There is an increasing body of evidence to suggest that inhibition of complement activation may be a valuable approach to avert hyperacute rejection. In our study, the guinea-pig to rat discordant kidney xenograft model was adapted for the investigation of renal transplant function and an attempt was made to delay the hyperacute rejection using systemically administered cobra venom factor (CVF) and soluble complement receptor type 1 (sCR1). The saline-treated control recipients experienced a rapid transplant rejection with a xenograft survival averaging 10.5 +/- 2.1 min. Administration of a single 60 U/kg i.v. bolus of CVF significantly prolonged renal graft survival to 20.4 +/- 2.5 h, and by a single bolus of sCR1 (50 mg/kg) a prolongation of graft survival to 18.8 +/- 2.3 h was achieved. The grafts functioned only over periods of 2.5 +/- 0.3 and 2.3 +/- 0.2 h, respectively. No complications of sCR1 were noted. We concluded that complement inhibition by sCR1 may be an important component in the therapeutic approach aiming at the prevention of hyperacute rejection in human organ transplantation.

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