Alloimmune induction of endothelial cell-derived interferon-γ-inducible chemokines

Raghavanpillai Raju, Angela Malloy, Tara Shah, Rodney Smith, Martin Oaks, Jeffrey D. Hosenpud

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Background. The interaction between host lymphocytes and endothelial cells on the transplanted organ is believed to play an important role in acute and chronic graft rejection. Trafficking and recruitment of lymphocytes to the site of inflammation is known to be controlled by several cytokines and chemokines. It is unclear whether endothelial cells themselves can be a source of inflammatory chemoattractant molecules on alloimmune induction. Methods. Using a semiquantitative polymerase chain reaction method, the authors analyzed the expression of chemokine mRNA coding for interferon (IFN)-γ-induced protein 10 (IP-10) and monokine induced by IFN-γ (Mig) in a pool of human aortic endothelial cells. Both of these chemokines are known to be induced by IFN-γ. Endothelial cell-derived chemokine mRNA was assayed at rest, after IFN-γ activation, and after co-culture with allogeneic peripheral blood mononuclear cells (PBMC) from normal blood donors with and without a monoclonal antibody to IFN-γ. Finally, protein release into the media was assayed using an enzyme-linked immunosorbent assay to IP-10. Results. Mig and IP-10 were expressed in human endothelial cells both after IFN-γ treatment and after PBMC co-culture. Furthermore, the expression of both of these endothelial cell-derived chemokines was dependent on IFN-γ because PBMC-induced expression was blocked with anti-IFN-γ. IP-10 levels in the endothelial cell supernatant increased from a baseline of 13.4±10.8 pg/mL to 299.5±13.4 pg/mL (P<0.0001) with exposure to PBMC and was likewise inhibited by anti-IFN-γ A-b (33.8±17.8 pg/mL). Conclusions. Vascular endothelial cells are capable of producing inflammatory chemokines when activated and potentially serve to amplify the allogeneic response.

Original languageEnglish (US)
Pages (from-to)1072-1074
Number of pages3
JournalTransplantation
Volume75
Issue number7
DOIs
StatePublished - Apr 15 2003
Externally publishedYes

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ASJC Scopus subject areas

  • Transplantation

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