The Effect of Soluble Complement Receptor Type 1 on Hyperacute Rejection of Porcine Xenografts

Pruitt, Scott K.; Kirk, Allan D.; Bollinger, R. Randal; Marsh, Henry C.; Collins, Bradley H.; Levin, Jeffrey S.; Mault, James R.; Heinle, Jeffrey S.; Ibrahim, Sherif; Rudolph, Abby E.; Baldwin, William M.; Sanfilippo, Fred

doi:10.1097/00007890-199402150-00009

Cited by 247 publications

(104 citation statements)

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“…Porcine hearts were transplanted into cynomolgus monkeys as previously described (32). On the day before transplantation, human Ig 2 g/kg was administered to the monkeys through a dual lumen Hickman catheter (Bard Access Systems, Salt Lake City, UT) placed in the right internal jugular vein.…”

Section: Methodsmentioning

confidence: 99%

Immunoglobulin prevents complement-mediated hyperacute rejection in swine-to-primate xenotransplantation.

et al. 1995

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Immunoglobulins regulate the complement system by activating complement on foreign surfaces and diverting reactive complement proteins away from autologous cell surfaces. Based on this model, we explored the ability of Ig to balance complement activation versus control in a pig-toprimate cardiac xenotransplantation model in which the binding of xenoreactive antibodies of the recipient to graft blood vessels and the activation of complement cause hyperacute rejection. Human IgG added to human serum caused a dose-dependent decrease in deposition of iC3b, cytotoxicity, and heparan sulfate release when the serum was incubated with porcine endothelial cells. This decrease was not caused by alteration in antibody binding or consumption of complement but presumably reflected decreased formation of C3 convertase on the endothelial cells. Infusion of purified human IgG into nonhuman primates prevented hyperacute rejection of porcine hearts transplanted into the primates. As expected, the transplants contained deposits of recipient Ig and Clq but not other complement components. The inhibition of complement on endothelial cell surfaces and in the xenotransplantation model supports the idea that IgG regulates the classical complement pathway and supports therapeutic use of that agent in humoral-mediated disease. (J. Clin. Invest. 1995Invest. .96:2404Invest. -2412

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Section: Methodsmentioning

confidence: 99%

Immunoglobulin prevents complement-mediated hyperacute rejection in swine-to-primate xenotransplantation.

et al. 1995

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“…sCR1 prolonged the survival of porcine cardiac xenografts perfused with human blood (82). Beside this model, dose dependent prolongation of xenograft survival has been seen in several other animal models (83,84).…”

Section: Hyperacute Rejectionmentioning

confidence: 70%

Pharmacological manipulation of the complement system in human diseases

Asghar¹

1996

Front Biosci

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“…1B). Histopathologically, the rejected hearts showed features of DXR typically seen in discordant combinations when hyperacute rejection is averted by depletion of complement (46,47), or by genetic modification of donor pig organs to express human complementregulating proteins (9,48,49).…”

Section: Discussionmentioning

confidence: 99%

Long-Term Survival of Hamster Hearts in Presensitized Rats

Lin

Soares

Sato

et al. 2000

The Journal of Immunology

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We transplanted hamster hearts into rats that had been sensitized to hamster cardiac grafts 5 days earlier as a model for discordant xenotransplantation. Sensitized rats had high serum levels of elicited anti-donor IgM and IgG that caused hyperacute rejection. Transient complement inhibition with cobra venom factor (CVF) plus daily and continuing cyclosporin A (CyA) prevented hyperacute rejection. However, grafts underwent delayed xenograft rejection (DXR). DXR involved IgG and associated Ab-dependent cell-mediated rejection, because depletion of IgG or Ab-dependent cell-mediated rejection-associated effector cells prolonged graft survival and the serum-mediated Ab-dependent cell-mediated cytotoxicity in vitro. Blood exchange in combination with CVF/CyA treatment dramatically decreased the level of preexisting Abs, but DXR still occurred in association with the return of Abs. Splenectomy and cyclophosphamide acted synergistically to delay Ab return, and when combined with blood exchange/CVF/CyA facilitated long-term survival of grafts. These grafts survived in the presence of anti-donor IgM, IgG, and complement that precipitated rejection of naive hearts, indicating that accommodation (survival in the presence of anti-graft Abs and complement) had occurred. We attribute the long-term survival to the removal of preexisting anti-donor Abs and therapy that attenuated the rate of Ab return. Under such conditions, the surviving hearts showed expression in endothelial cells and smooth muscle cells of protective genes and an intragraft Th2 immune response. Th2 responses and protective genes are associated with resistance to IgM- and IgG-mediated, complement-dependent and -independent forms of rejection.

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The Effect of Soluble Complement Receptor Type 1 on Hyperacute Rejection of Porcine Xenografts

Cited by 247 publications

References 0 publications

Immunoglobulin prevents complement-mediated hyperacute rejection in swine-to-primate xenotransplantation.

Immunoglobulin prevents complement-mediated hyperacute rejection in swine-to-primate xenotransplantation.

Pharmacological manipulation of the complement system in human diseases

Long-Term Survival of Hamster Hearts in Presensitized Rats

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