Dextran sulfate facilitates anti-CD4 mAb-induced long-term rat cardiac allograft survival after prolonged cold ischemia

Gajanayake, T; Sawitzki, B; Matozan, K; Korchagina, E Y; Lehmann, M; Volk, H-D; Rieben, R (2008). Dextran sulfate facilitates anti-CD4 mAb-induced long-term rat cardiac allograft survival after prolonged cold ischemia. American journal of transplantation, 8(6), pp. 1151-62. Oxford: Wiley-Blackwell 10.1111/j.1600-6143.2008.02239.x

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Ischemia/reperfusion injury leads to activation of graft endothelial cells (EC), boosting antigraft immunity and impeding tolerance induction. We hypothesized that the complement inhibitor and EC-protectant dextran sulfate (DXS, MW 5000) facilitates long-term graft survival induced by non-depleting anti-CD4 mAb (RIB 5/2). Hearts from DA donor rats were heterotopically transplanted into Lewis recipients treated with RIB 5/2 (20 mg/kg, days-1,0,1,2,3; i.p.) with or without DXS (grafts perfused with 25 mg, recipients treated i.v. with 25 mg/kg on days 1,3 and 12.5 mg/kg on days 5,7,9,11,13,15). Cold graft ischemia time was 20 min or 12 h. Median survival time (MST) was comparable between RIB 5/2 and RIB 5/2+DXS-treated recipients in the 20-min group with >175-day graft survival. In the 12-h group RIB 5/2 only led to chronic rejection (MST = 49.5 days) with elevated alloantibody response, whereas RIB 5/2+DXS induced long-term survival (MST >100 days, p < 0.05) with upregulation of genes related to transplantation tolerance. Analysis of the 12-h group treated with RIB 5/2+DXS at 1-day posttransplantation revealed reduced EC activation, complement deposition and inflammatory cell infiltration. In summary, DXS attenuates I/R-induced acute graft injury and facilitates long-term survival in this clinically relevant transplant model.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Herz und Gefässe

UniBE Contributor:

Matozan, Katja and Rieben, Robert

ISSN:

1600-6135

ISBN:

18444916

Publisher:

Wiley-Blackwell

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:06

Last Modified:

04 May 2014 23:20

Publisher DOI:

10.1111/j.1600-6143.2008.02239.x

PubMed ID:

18444916

Web of Science ID:

000256347100010

URI:

https://boris.unibe.ch/id/eprint/28547 (FactScience: 121270)

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