Prevention of Hyperacute Rejection by Human Decay Accelerating Factor in Xenogeneic Perfused Working Hearts

Schmoeckel, Michael; Nollert, Georg; Shahmohammadi, Michael; Young, Vincent; Chavez, Gilda; Kasper-König, W.; White, David J.; Müller‐Höcker, Josef; Arendt, R; Wilbert-Lampen, Ute; Hammer, C.; Reichart, B.

doi:10.1097/00007890-199609270-00005

Cited by 64 publications

(25 citation statements)

References 9 publications

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“…These proteins inhibit steps in the complement cascade, and although the natural antibodies will still be bound to the ␣-Gal antigen, cell lysis would be prevented. Several transgenic pig herds have been developed expressing one (e.g., CD55 [104]) or more genes encoding human complement-regulatory proteins.…”

Section: Genetically Engineered Pigsmentioning

confidence: 99%

Infectious Disease Issues in Xenotransplantation

Chapman

Switzer

Sandstrom

et al. 2014

Emerging Infections 3

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Section: Genetically Engineered Pigsmentioning

confidence: 99%

Infectious Disease Issues in Xenotransplantation

Chapman

Switzer

Sandstrom

et al. 2014

Emerging Infections 3

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“…Further, a recent study on the activity of IL-6 in the differentiation of monocytes to macrophages and dendritic cells has shown that IL-6 inhibits the differentiation of monocytes to dendritic cells by promoting their differentiation toward macrophages [25]. In addition, IL-6 has been used as a marker of mononuclear cell activation in a recent study investigating the protective effect of human decay accelerating factor in a porcine hearts perfused by human blood [40].…”

Section: > Imentioning

confidence: 99%

Interleukin-6 in islet xenograft rejection

Benda¹,

Korsgren²

2001

Transplant Int

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Earlier work on primate cardiac xenotransplantation has demonstrated a correlation between interleukin (1L)-6 levels and severity of vascular rejection. IL-6 was originally identified as a lymphokine inducing final maturation of B lymphocytes into antibody-secreting cells. The present study aimed to evaluate the role of IL-6 in fetal porcine islet-like cell cluster (ICC) xenograft rejection. Moreover, other authors have reported that eosinophils dominate the cellular response following discordant islet xenograft transplantation. Here, a technique for specific detection of eosinophils was applied. IL-6-deficient mice and wild-type controls were implanted with fetal porcine ICCs under the kidney capsule and killed 4-, 7-, and 10 days after transplantation. Xenografts were histologically evaluated, and serum samples were analyzed for IgM and IgG antibodies against ICC membrane antigens. IL-6-deficient mice and wild-type controls readily rejected the xenograft. On day 7 after transplantation, abundant numbers of F4/ 80' and Mac-l+ cells were found distributed throughout the collapsing graft accompanied by small amounts of eosinophils and peripherally accumulated CD3' T cells (predominantly CD4'). Significantly lower serum levels of IgM and IgG antibodies against ICC membrane antigens were observed in IL-6-deficient mice on day 4 or 7 after transplantation when compared to wild-type controls. No significant differences were seen on day 10 after transplantation. In both experimental groups, specific IgM and IgG antibody levels remained stable over time. In the pig-to-mouse model, IL-6 seems to be of minor importance to fetal porcine ICC xenograft rejection. Macrophages, and not eosinophils, dominate the cellular response associated with this process.

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“…In the same time, numerous extracorporeal models and a working heart device were developed in order to investigate HAR and the immunological reactions also in transgenic pig hearts [113]. The transplantation of h-DAF transgenic pig hearts to the abdominal aorta of cynomolgus monkeys resulted in a beating time of up to 62 days, mean 42 days [65].…”

Section: Xenogenic Heart Transplantationmentioning

confidence: 99%

Organs from Animals for Man

Hammer¹,

Linke²,

Wagner³

et al. 1998

Int Arch Allergy Immunol

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In the following review some of the problems of xenotransplantation shall be discussed, based on the few experimental data available so far and on reports in the literature describing investigations which may be of importance for xenotransplantation. The impact of gravity on the upright posture of man versus almost all other mammals, the dysfunction between enzymes and hormones in different species and the lack of interactions between interleukins, cytokines and vasoactive substances will be taken into consideration. The question must be asked whether different levels of carrier molecules or serum proteins play a role in the physiological network. Even though the development of transgenic animals or other imaginative manipulations may lead to the acceptance of any type of xenografted organ, it has to be established for how long the products of the xenografts are able to act in the multifactorial orchestra. We are far from understanding xenogeneic molecular mechanisms involved in toxicity, necrosis and apoptosis or even reperfusion injury and ischemia in addition to the immediate mechanisms of the hyperacute xenogeneic rejection. Here, cell adhesion, blood clotting and vasomotion collide and bring micro- and macrocirculation to a standstill. All types of xenogeneic immunological mechanisms studied so far were found to have a more serious impact than those seen in allogeneic transplantation. In addition we are now only beginning to understand that so-called immunological parameters in allogeneic mechanisms act also in a true physiological manner in the xenogeneic situation. These molecular mechanisms occur behind the curtain of hyperacute, accelerated, acute or chronic xenograft rejection of which only some folds have been lifted to allow glimpses of part of the total scene. Other obstacles are likely to arise when long-term survival is achieved. These obstacles include retroviral infections, transfer of prions and severe side effects of the massive immunosuppression which will be needed. Moral, ethical and religious concerns are under debate and the species-specific production of proteins of the foreign donor species developed for clinical use suddenly appears to be a greater problem than anticipated.

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Prevention of Hyperacute Rejection by Human Decay Accelerating Factor in Xenogeneic Perfused Working Hearts

Cited by 64 publications

References 9 publications

Infectious Disease Issues in Xenotransplantation

Infectious Disease Issues in Xenotransplantation

Interleukin-6 in islet xenograft rejection

Organs from Animals for Man

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