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Endothelium targeted anti‐complement therapy protects renal allografts by modulating T cell response
Author(s) -
Maldonado Claudio,
Pushpakumar Sathnur,
Soni Chirag V.,
Perez-Abadia Gustavo
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1051.3
Subject(s) - complement system , immune system , immunology , transplantation , medicine , endothelium , inflammation , cell , kidney , flow cytometry , biology , genetics
Complement activation and its components are pathogenic mediators of reperfusion injury and cell‐mediated organ rejection. Complement‐mediated endothelial cell activation and T cell interactions lead to the production of bioactive substances that enhance cell‐mediated immune response. The objective was to determine whether an endothelium‐targeted anti‐complement therapy would reduce the acute rejection response in allografts. We hypothesized that bolstering complement defenses on the endothelial barrier prior to transplantation reduces: inflammation, immune cell infiltration, and the severity of acute rejection. Fisher to Lewis kidney transplants were performed with a warm ischemia of 60 min. Allograft endothelium was decorated with an anti‐complement protein, vaccinia virus complement control protein (VCP), using a liposome‐based delivery system placed in an organ preservation solution. Animals were followed for 12 days. Assessment included renal function, histology and flow cytometry to quantify lymphocyte and T cell populations in allografts. Allografts decorated with VCP had reduced: renal dysfunction, antigen presenting cells and activated T cells. We conclude that complement blockade at the allograft's endothelial barrier reduces infiltration of immune cells during acute rejection and improves allograft outcome. Support provided by NIH grant 1R42HL079855 and EndoProtech, Inc.