Inhibition of the Cytolytic Protein Perforin Prevents Rejection of Transplanted Bone Marrow Stem Cells in Vivo
Julie A Spicer, Christian K Miller, Patrick D O'Connor, Jiney Jose, Anna C Giddens, Jagdish K Jaiswal, Stephen MF Jamieson, Matthew R Bull, William A Denny, Hedieh Akhlaghi, Joseph A Trapani, Geoff R Hill, Karshing Chang, Kate H Gartlan
Journal of Medicinal Chemistry | AMER CHEMICAL SOC | Published : 2020
Perforin is a key effector protein in the vertebrate immune system and is secreted by cytotoxic T lymphocytes and natural killer cells to help eliminate virus-infected and transformed target cells. The ability to modulate perforin activity in vivo could be extremely useful, especially in the context of bone marrow stem cell transplantation where early rejection of immunologically mismatched grafts is driven by the recipient's natural killer cells, which overwhelmingly use perforin to kill their targets. Bone marrow stem cell transplantation is a potentially curative treatment for both malignant and nonmalignant disorders, but when the body recognizes the graft as foreign, it is rejected by t..View full abstract
Awarded by Wellcome Trust
This work was supported by the Wellcome Trust (Grant 092717) and the Auckland Division of the Cancer Society of New Zealand. The authors also acknowledge the invaluable contribution made by Dr. David Middlemiss to this project. Sisira Kumara and Karin Tan carried out HPLC studies, and Dr. Lydia Liew and Dr. Adrian Blaser conducted all NMR experiments.