To Örebro University

oru.seÖrebro University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Post‐transplant upregulation of chemokine messenger RNA in non‐human primate recipients of intraportal pig islet xenografts
Diabetes Institute for Immunology and Transplantation, Department of Surgery, Universityof Minnesota, Minneapolis MN, USA; Department of Clinical Immunology, Rudbeck Laboratory, UppsalaUniversity Hospital, Uppsala, Sweden.ORCID iD: 0000-0002-3671-5046
Department of Veterinary and Biomedical Sciences, University of Minnesota, St Paul, MN, USA.
Diabetes Institute for Immunology and Transplantation, Department of Surgery, University of Minnesota, Minneapolis MN, USA.
Departmentof Veterinary and Biomedical Sciences, University ofMinnesota, St Paul, MN, USA.
Show others and affiliations
2005 (English)In: Xenotransplantation, ISSN 0908-665X, E-ISSN 1399-3089, Vol. 12, no 4, p. 293-302Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: We have previously shown that pig-to-primate intraportal islet xenografts reverse diabetes, escape hyperacute rejection, and undergo acute cellular rejection in non-immunosuppressed recipients. To gain a better understanding of mechanisms contributing to xenoislet rejection in non-human primates we examined gene expression in livers bearing islet xenografts in the first 72 h after transplantation.

METHODS: Liver specimens were collected at sacrifice from seven non-immunosuppressed rhesus macaques at 12, 24, 48 and 72 h after intraportal porcine islet transplantation. Following total RNA extraction, mRNA was quantified using SYBR green real-time reverse transcription polymerase chain reaction (RT-PCR) for species-specific immune response genes. Data were analyzed using comparative cycle threshold (Ct) analysis, adjusted for specific primer-efficiencies and normalized to cyclophilin expression.

RESULTS: Porcine insulin mRNA was detected in all liver samples. Cluster analysis revealed differential gene expression patterns at 12 and 24 h (early) compared with at 48 and 72 h (late) post-transplant. Gene expression patterns were associated with histological findings of predominantly neutrophils and only a few lymphocytes at 12 and 24 h and an increasing number of lymphocytes and macrophages at 48 and 72 h. Transcript levels of CXCR3 and its ligands, interferon-inducible protein 10 (IP-10) and monokine induced by IFN-gamma (Mig), significantly increased between early and late time points together with expression of MIP-1alpha, regulated on activation normal T expressed and secreted protein (RANTES) and MCP-1. CCR5 showed only a marginal, non-significant increase. Fas ligand, perforin and granzyme B transcripts were all elevated at 48 and 72 h post-transplant.

CONCLUSIONS: Our data suggest that CXCR3, with ligands IP-10 and Mig, is involved in T cell recruitment in acute islet xenograft rejection in non-human primates. Upregulation of RANTES and MIP-1alpha transcripts in the absence of a significant CCR5 increase suggests a possible involvement of other chemokine receptors. MCP-1 expression is associated with T cell and macrophage infiltration. Elevated cytotoxic effector molecule expression (Fas ligand, perforin, granzyme B) indicates T-cell mediated graft destruction by cytotoxic and cytolytic mechanisms within 48 to 72 h after transplantation. These results identify the CXCR3-mediated chemoattractant pathway as an immunosuppressive target in pig-to-primate islet xenotransplantation.

Place, publisher, year, edition, pages
John Wiley & Sons, 2005. Vol. 12, no 4, p. 293-302
National Category
Immunology in the medical area
Identifiers
URN: urn:nbn:se:oru:diva-111597DOI: 10.1111/j.1399-3089.2005.00228.xISI: 000229637300006PubMedID: 15943778Scopus ID: 2-s2.0-20944446344OAI: oai:DiVA.org:oru-111597DiVA, id: diva2:1837836
Available from: 2024-02-15 Created: 2024-02-15 Last updated: 2024-02-19Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMedScopus

Authority records

Hårdstedt, Maria

Search in DiVA

By author/editor
Hårdstedt, Maria
In the same journal
Xenotransplantation
Immunology in the medical area

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 9 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf