Camouflaging endothelial cells: does it prolong graft survival?
Camouflaging antigens on the surface of cells seems an appealing way to prevent activation of the immune system. We explored the possibility of preventing hyperacute rejection by chemically camouflaging endothelial cells (EC). In vitro as well as in vivo experiments were performed. First, the ability of mPEG coating to prevent antibody-antigen interactions was evaluated. Second, we tested the degree to which mPEG coating prevents activation of EC by stimuli such as TNF-alpha and LPS. Third, in vivo experiments were performed to test the ability of mPEG coating to prolong xenograft survival. We demonstrate that binding of several antibodies to EC or serum proteins can be inhibited by mPEG. Furthermore, binding of TNF-alpha as well as LPS to EC is blocked since mPEG treatment of EC inhibits the subsequent up-regulation of E-selectin by these stimuli. However, in vivo experiments revealed that currently this method alone is not sufficient to prevent hyperacute rejection.
Stuhlmeier
K M
KM
Immunobiology Research Center, Beth Israel Deaconess Medical Center, Harvard Medical School, 99 Brookline Ave., Boston, MA 02215, USA. kstuhlme@bidmc.harvard.edu
Lin
Y
Y
D000818:Animals; D000937:Antigen-Antibody Reactions / Q000187:drug effects; D003176:Complement C3 / Q000032:analysis / Q000276:immunology; D006224:Cricetinae; D019040:E-Selectin / Q000032:analysis; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology*; D006084:Graft Rejection / Q000517:prevention & control*; D016027:Heart Transplantation; D007075:Immunoglobulin M / Q000032:analysis / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D008647:Mesocricetus; D016328:NF-kappa B / Q000276:immunology; D010477:Perfusion; D011092:Polyethylene Glycols / Q000494:pharmacology*; D051381:Rats; D013552:Swine; D013997:Time Factors; D014181:Transplantation Immunology; D014183:Transplantation, Heterologous; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology
D003176:Complement C3; D019040:E-Selectin; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol