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DC Field | Value | Language |
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dc.contributor.author | Nikolic-Paterson D.J. | en |
dc.contributor.author | Han Y. | en |
dc.contributor.author | Tesch G.H. | en |
dc.contributor.author | DI Paolo J. | en |
dc.contributor.author | Mulley W.R. | en |
dc.contributor.author | Kanellis J. | en |
dc.contributor.author | Ma F.Y. | en |
dc.contributor.author | Ramessur Chandran S. | en |
dc.date.accessioned | 2021-05-14T13:27:09Z | en |
dc.date.available | 2021-05-14T13:27:09Z | en |
dc.date.copyright | 2017 | en |
dc.date.created | 20170816 | en |
dc.date.issued | 2017-08-16 | en |
dc.identifier.citation | Transplantation. 101 (8) (pp e240-e248), 2017. Date of Publication: 01 Aug 2017. | en |
dc.identifier.issn | 0041-1337 | en |
dc.identifier.uri | https://repository.monashhealth.org/monashhealthjspui/handle/1/39421 | en |
dc.description.abstract | Background Organ transplantation into sensitized patients with preexisting donor-specific antibodies (DSA) is very challenging. Spleen tyrosine kinase (Syk) promotes leukocyte recruitment and activation via signaling through various cell surface receptors. We investigated whether a selective Syk inhibitor (GS-492429) could suppress antibody-mediated rejection (AMR) in a rat model of AMR in sensitized recipients. Methods Recipient Lewis rats (RT1l) were immunized with donor (Dark Agouti, RT1av1) spleen cells (day -5). Recipients underwent bilateral nephrectomy and orthotopic renal transplantation (day 0). Cellular rejection was minimized by tacrolimus treatment from day -1. Groups received GS-492429 (30 mg/kg, twice a day) (n = 11) or vehicle (n = 12) from 1 hour before transplantation until being killed on day 3. Results Vehicle-treated recipients developed graft dysfunction on day 1 which rapidly worsened by day 3. Histology showed severe damage (thrombosis, acute tubular injury, capillaritis) and infiltration of many Syk+ leukocytes. GS-492429 did not affect graft dysfunction on day 1, but treatment reduced allograft damage and prevented the rapid deterioration of graft function on day 3. GS-492429 reduced the prominent macrophage infiltrate and reduced the M1 proinflammatory response. Neutrophil and NK cell infiltration and capillary thrombosis were also significantly reduced by GS-492429 treatment. Serum DSA levels and the deposition of IgG and C4d in the allograft were equivalent in the 2 groups. Conclusions Treatment with a Syk inhibitor significantly reduced renal allograft injury in a model of severe antibody-mediated damage in highly sensitized recipients. Further studies are warranted to determine whether Syk inhibition is a potential adjunctive treatment in clinical AMR.Copyright © 2017 Wolters Kluwer Health, Inc. | en |
dc.language | en | en |
dc.language | English | en |
dc.publisher | Lippincott Williams and Wilkins (E-mail: kathiest.clai@apta.org) | en |
dc.relation.ispartof | Transplantation | en |
dc.title | Inhibition of Spleen Tyrosine Kinase Reduces Renal Allograft Injury in a Rat Model of Acute Antibody-Mediated Rejection in Sensitized Recipients. | en |
dc.type | Article | en |
dc.identifier.affiliation | Nephrology | en |
dc.identifier.doi | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1097/TP.0000000000001826 | en |
dc.publisher.place | United States | en |
dc.identifier.pubmedid | 28594748 [http://www.ncbi.nlm.nih.gov/pubmed/?term=28594748] | en |
dc.identifier.source | 616739930 | en |
dc.identifier.institution | (Ramessur Chandran, Han, Tesch, Mulley, Kanellis, Ma, Nikolic-Paterson) Department of Nephrology, Monash Medical Centre, Clayton, VIC, Australia (Ramessur Chandran, Han, Tesch, Mulley, Kanellis, Ma, Nikolic-Paterson) Monash University Centre for Inflammatory Diseases, Monash Medical Centre, Clayton, VIC, Australia (DI Paolo) Gilead Sciences, Foster City, CA, United States | en |
dc.description.address | D.J. Nikolic-Paterson, Department of Nephrology, Monash Medical Centre, Clayton, VIC, Australia. E-mail: david.nikolic-paterson@monash.edu | en |
dc.description.publicationstatus | Embase | en |
dc.rights.statement | Copyright 2017 Elsevier B.V., All rights reserved. | en |
dc.identifier.authoremail | Nikolic-Paterson D.J.; david.nikolic-paterson@monash.edu | en |
dc.identifier.affiliationext | (DI Paolo) Gilead Sciences, Foster City, CA, United States | - |
dc.identifier.affiliationmh | (Ramessur Chandran, Han, Tesch, Mulley, Kanellis, Ma, Nikolic-Paterson) Department of Nephrology, Monash Medical Centre, Clayton, VIC, Australia (Ramessur Chandran, Han, Tesch, Mulley, Kanellis, Ma, Nikolic-Paterson) Monash University Centre for Inflammatory Diseases, Monash Medical Centre, Clayton, VIC, Australia | - |
item.cerifentitytype | Publications | - |
item.fulltext | No Fulltext | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.grantfulltext | none | - |
item.openairetype | Article | - |
crisitem.author.dept | Nephrology | - |
Appears in Collections: | Articles |
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