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

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

Research output: Contribution to journalArticle

8 Citations (Scopus)

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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Chemokines
Interferons
Endothelial Cells
Blood Cells
Coculture Techniques
Proteins
Lymphocytes
Monokines
Messenger RNA
Chemotactic Factors
Graft Rejection
Blood Donors
Cell Culture Techniques
Enzyme-Linked Immunosorbent Assay
Monoclonal Antibodies
Cytokines
Inflammation
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Transplantation

Cite this

Alloimmune induction of endothelial cell-derived interferon-γ-inducible chemokines. / Raju, Raghavan Pillai; Malloy, Angela; Shah, Tara; Smith, Rodney; Oaks, Martin; Hosenpud, Jeffrey D.

In: Transplantation, Vol. 75, No. 7, 15.04.2003, p. 1072-1074.

Research output: Contribution to journalArticle

Raju, Raghavan Pillai ; Malloy, Angela ; Shah, Tara ; Smith, Rodney ; Oaks, Martin ; Hosenpud, Jeffrey D. / Alloimmune induction of endothelial cell-derived interferon-γ-inducible chemokines. In: Transplantation. 2003 ; Vol. 75, No. 7. pp. 1072-1074.
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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.",
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