The free radical scavenger S‐PBN significantly prolongs DSG‐mediated graft survival in experimental xenotransplantation

Biglarnia, Ali-Reza; Emanuelsson, Cecilia; Quach, My; Clausen, Fredrik; Larsson, Erik; Schneider, Mårten K J; Tufveson, Gunnar; Lorant, Tomas

doi:10.1111/j.1399-3089.2012.00700.x

Cited by 3 publications

(3 citation statements)

References 32 publications

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“…2 AHXR occurs within 3 days after transplantation in the mouse-to-rat and hamster-to-rat heart transplantation models, characterized by binding of different immunoglobulins (Ig) to the vascular endothelium, vasculitis, thrombosis, tissue destruction, and edema. 3 Turnquist et al 4 observed a potent ability of interleukin (IL)-33 to increase suppressive CD4 + Foxp3 + regulatory T cells (Tregs). Overall, fewer infiltrated T cells, but increased numbers of Tregs, were seen in the heart grafts.…”

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confidence: 99%

“…To confirm the hypothesis, we used the concordant mouse-to-rat transplantation model, where the donor heart is heterotopically transplanted to the neck vessels of the recipient. 3 The combined use of IL-33 and Lef thus allowed us to study the impact of IL-33 on AVR. 13 Graft survival was determined in separate animals, and the activation and infiltration of immune cells were studied separately by flow cytometry.…”

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confidence: 99%

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Recombinant IL-33 prolongs leflunomide-mediated graft survival by reducing IFN-γ and expanding CD4+Foxp3+ T cells in concordant heart transplantation

Dai

Jin

et al. 2016

Laboratory Investigation

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Interleukin (IL)-33 is a novel IL-1 family member, and its administration has been associated with promotion of T helper type-2 (Th2) cell activity and cytokines, particularly IL-4 and IL-5 in vivo. Recently, IL-33 was shown to increase CD4 + Foxp3 + regulatory T cells (Tregs) and to suppress levels of the Th1-type cytokine IFN-γ in allogeneic heart transplantation in mice. Therefore, we hypothesized that IL-33 and leflunomide (Lef) could prolong graft survival in the concordant mouse-to-rat heart transplantation model. In this model, xenografts undergo acute humoral xenograft rejection (AHXR) typically on day 3 or cell-mediated rejection approximately on day 7 if AHXR is inhibited by Lef treatment. Recipients were treated with Lef (n = 6), IL-33 (n = 6), IL-33 combined with Lef (n = 6), or left untreated (n = 6) for survival studies. Heart grafts were monitored until they stopped beating. Mouse heterotopic grafts were performed, and recipients were sacrificed on days 2 and 7 for histological and flow cytometric analyses. The combination of IL-33 and Lef significantly prolonged the grafts from 17.3 ± 2.3 to 2.8 ± 0.4 days, compared to untreated controls. IL-33 administration with Lef, while facilitating Th2-associated cytokines (IL-4 on day 2 but not day 7), also decreased IFN-γ on day 2 and day 7, compared with Lef treatment only. Furthermore, IL-33 with Lef administration caused an expansion of suppressive CD4 + Foxp3 + Tregs in rats. The IL-33 and Lef combination therapy resulted in significantly prolonged graft survival, associated with markedly decreased Th1 cells and increased IL-10 levels. In addition, the combination therapy significantly decreased the percentage of CD-45 + B cells on days 2 and 7, compared with monotherapy. These findings reveal a new immunoregulatory property of IL-33. Specifically, it facilitates regulatory cells, particularly functional CD4 + Foxp3 + Tregs that underlie IL-33-mediated cardiac xenograft survival. Moreover, it can decrease Th1 cells and cytokine expression of Th1 T cells in xenograft recipients, for example IFN-γ.

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confidence: 99%

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confidence: 99%

Recombinant IL-33 prolongs leflunomide-mediated graft survival by reducing IFN-γ and expanding CD4+Foxp3+ T cells in concordant heart transplantation

Dai

Jin

et al. 2016

Laboratory Investigation

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“…In experimental traumatic brain injury, S-PBN treatment reduced T-cell infiltration and adhesion-molecule expression on the endothelium. Biglarnia et al [10] hypothesized that S-PBN could also reduce infiltration of T cells during cell-mediated xenograft rejection and increase graft survival. To test this, a concordant mouse-to-rat heart transplantation model was used where recipients received no treatment or 15-deoxyspergualin (DSG) and S-PBN, alone or in combination.…”

Section: Small Animal Modelsmentioning

confidence: 99%