Our basic research lab is testing the hypothesis that kidney transplant rejection requires two major signals. The idea is that the immune system evolved to attack foreign antigens, which injure tissue. Ordinarily the foreign antigen is a pathogen, which injures tissue during infection. During transplant, we propose that the foreign antigen is the allograft, and the injury signal results from damage to the tissue during the transplant surgery. We have performed transplants between inbred strains of rats where there is no rejection. None-the-less the injury from the surgery resulted in the recruitment of dendritic cells into the transplant and the new expression of adhesion molecules and MHC Class II molecules on parenchymal tissues. In other studies, we find that in vitro models of ischemia reperfusion injury cause renal tubule cell lines to express chemokine and cytokine genes which might be important in initiating rejection.
We now have identified genes that are activated after ischemic renal injury. These genes cause an inflammatory response. We will determine if gene therapy of the renal transplant will prevent these genes from being activated and will prevent inflammation and rejection.
RESEARCH INTERESTS
transplant rejection
acute renal failure
perinatal infections
RECENT PUBLICATIONS
Lu, C.Y. and Senitko, M., "The inflammatory response to ischemic acute renal injury." Seldin and Giebisch?s The Kidney: Physiology and Pathophysiology. Academic Press. Ed. Alpern, R.J. and Hebert, S.C. Fourth edition. Academic Press., 2577-2590, 2008
D. Rohan Jeyarajah, M.L. Kielar, H. Saboorian, N.Frantz, C.Y. Lu., "Impact of bile duct obstruction on hepatic E. coli infection: role of IL10." Am J. Physiol. Gastrointest Liver PHysiol, 291:G91-94, 2006
Kielar, M.L.; John, R.; Bennett, M.; Richardson,J.A.; Shelton, J.M.; Chen, L.; Jeyarajah, D.R.; Zhous, X.J.; Zhou, H.; Chiquett, B.; Nagami, G.T.; Lu, C. Y., "The maladaptive role of interleukin 6 in ischemic acute renal failure." J. Am. Soc. Nephrol., 16:3315-3325, 2005
Zhang, Y., Woodward, V. K., Shelton, J. M., Richardson, J. A., Link, D. C., Zhou, X. J., Kielar, M. L., Jeyarajah, D. R. and Lu, C. Y., "Ischemia/ reperfusion induces G-CSF gene expression by renal medullary thick ascending limb cells in vivo and in vitro." Am J. Physiol - Renal Physiology, 286:F1193-201, 2004
SIGNIFICANT PUBLICATIONS
Lu, C.Y., Calamai, E.G. and Unanue, E.R., "A defect in the antigen-presenting function of macrophages from neonatal mice." Nature, 282:327-329, 1979
Redline, R.W. and Lu, C.Y., "The role of local immunosuppression in murine fetoplacental listeriosis." J. Clin. Invest., 79:1234-1241, 1987
Penfield, J.G., Y.Wang, S. Li, M.A. Kielar, S.C. Sicher, D.R. Jeyarajah, and Lu, C.Y., "Injury from transplant surgery recruits recipient MHC Class II-positive leukocytes, including dendritic cells, into the transplanted kidney in a rat model where there is no rejection." Kidney International, 56:1759-1769, 1999
Lu, C.Y., Penfield, J.G., Kielar, M.L., Vazquez, M.A., Jeyarajah, D.R, "Perspectives in basic science: Hypothesis: is renal allograft rejection initiated by the response to injury sustained during the transplant process?" Kidney International, 55:2157-2168, 1999
Lu, C.Y., J Hartono, M. Senitko, J. Chen., "The inflammatory response to ischemic acute kidney injury: a result of the ?right stuff? in the ?wrong place.?" Current Opinion in Nephrology & Hypertension, 16 (2):72-89, 2007
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