Date of Award
Master of Science
Microbiology and Immunology
Dr. Anthony Jevnikar
Osteopontin (OPN) is a multi-functional protein that can influence cell survival, chemotaxis and inflammation. The role of OPN produced by kidney tubular epithelial cell (TEC) following transplantation has not been defined. This study tests the role of OPN on the chemotaxis of Natural Killer (NK) cells, as well as the role of OPN as a survival factor for TECs in vitro and in vivo following kidney transplantation.
OPN-/- TECs had a substantially reduced capacity to attract NK cells in vitro when compared with OPN+/+TECs. OPN may only be an indirect regulator for the expression of NK specific chemokines in TECs, since recombinant mouse OPN had no direct chemotactic effect on NK cell migration. OPN did not alter survival of TECs when exposed to lethal doses of TNF-a, IFN-y and hypoxia.
Kidneys from OPN-/- mice (C57BL/6) were transplanted into MHC mismatched (Balb/c) nephrectomized recipients. OPN-/- kidney donor grafts resulted in significantly reduced survival and function when compared to OPN+/+ grafts. While the absence of OPN improves kidney ischemia reperfusion injury, possibly through an indirect effect on NK cell chemotaxis, the elimination of kidney expressed OPN may not benefit transplantation.
Shek, Kelvin, "The Regulation of Early and Late Renal Tubular Cell Injury by Osteopontin" (2011). Digitized Theses. 3575.