TY - JOUR
T1 - Modulation of IFN-γ-induced immunogenicity by phosphatidylethanolamine-linked hyaluronic acid
AU - Yard, Benito A.
AU - Yedgar, Saul
AU - Scheele, Martin
AU - Van Der Woude, Diane
AU - Beck, Grietje
AU - Heidrich, Bärbel
AU - Krimsky, Miron
AU - Van Der Woude, Fokko J.
AU - Post, Stefan
PY - 2002/3/27
Y1 - 2002/3/27
N2 - Background. The present study was conducted to examine the possibility of modulating interferon (IFN-γ)-induced immunogenicity by a novel compound that is composed of a PLA2 inhibitor linked to hyaluronic acid (HYPE). Methods. HYPE was tested for its effect on IFN-γ-induced expression of MHC class I, class II, and intercellular adhesion molecule (ICAM-1) in cultured endothelial and renal proximal tubular cells by flow cytometric analysis (FACS) as well as its ability to influence T cell activation in mixed lymphocyte reaction (MLR) or after mitogen stimulation. Results. In FACS, a profound inhibition in MHC class I and ICAM-1 staining was observed in stimulated or unstimulated cells that were incubated with HYPE. This was not due to down-regulation of antigen expression and only occurred when monoclonal antibodies, but not when polyclonal antibodies, were used. HYPE inhibited the induction of MHC class II in both cell types after IFN-γ stimulation in a dose-dependent manner. Moreover, the induction of class II transactivator (CIITA) was completely inhibited under these conditions, most likely because it blocked the binding of IFN-γ to the cell membrane. Addition of HYPE to MLR inhibited the proliferation of T cells and the secretion of interleukin (IL)-2, IFN-γ, and IL-10. This was not observed when HYPE was added together with anti-CD3 or phytohemagglutinin (PHA). Conclusion. Our study provides experimental evidence that HYPE has immunosuppressive features. This makes the compound an interesting candidate as an immunosuppressive drug, not only in organ transplantation, but also in diseases where IFN-γ is overexpressed.
AB - Background. The present study was conducted to examine the possibility of modulating interferon (IFN-γ)-induced immunogenicity by a novel compound that is composed of a PLA2 inhibitor linked to hyaluronic acid (HYPE). Methods. HYPE was tested for its effect on IFN-γ-induced expression of MHC class I, class II, and intercellular adhesion molecule (ICAM-1) in cultured endothelial and renal proximal tubular cells by flow cytometric analysis (FACS) as well as its ability to influence T cell activation in mixed lymphocyte reaction (MLR) or after mitogen stimulation. Results. In FACS, a profound inhibition in MHC class I and ICAM-1 staining was observed in stimulated or unstimulated cells that were incubated with HYPE. This was not due to down-regulation of antigen expression and only occurred when monoclonal antibodies, but not when polyclonal antibodies, were used. HYPE inhibited the induction of MHC class II in both cell types after IFN-γ stimulation in a dose-dependent manner. Moreover, the induction of class II transactivator (CIITA) was completely inhibited under these conditions, most likely because it blocked the binding of IFN-γ to the cell membrane. Addition of HYPE to MLR inhibited the proliferation of T cells and the secretion of interleukin (IL)-2, IFN-γ, and IL-10. This was not observed when HYPE was added together with anti-CD3 or phytohemagglutinin (PHA). Conclusion. Our study provides experimental evidence that HYPE has immunosuppressive features. This makes the compound an interesting candidate as an immunosuppressive drug, not only in organ transplantation, but also in diseases where IFN-γ is overexpressed.
UR - http://www.scopus.com/inward/record.url?scp=0037181442&partnerID=8YFLogxK
U2 - 10.1097/00007890-200203270-00028
DO - 10.1097/00007890-200203270-00028
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C2 - 11923705
AN - SCOPUS:0037181442
SN - 0041-1337
VL - 73
SP - 984
EP - 992
JO - Transplantation
JF - Transplantation
IS - 6
ER -