There is accumulating evidence that allograft rejection and certain other manifestations of cell-mediated immunity involve, in part, the interaction of T lymphocytes and endothelial cells. The importance of endothelial cells in immune responses to organ grafts derives from their interposition between inflammatory cells and target tissues, their ability to function as antigen-presenting cells and their ability to undergo a series of changes termed """"""""activation"""""""" which eventuate certain of the pathological and clinical manifestations of cell-mediated immunity. Heparan sulfate proteoglycan is a biologically active component of endothelial cell membranes and extracellular matrices. It has a role in many of the normal functions of blood vessels including the maintenance of a barrier to egress of blood cells and plasma proteins, and the prevention of thrombosis. The loss of heparan sulfate from endothelium has been thought to contribute to the pathogenesis of allograft rejection, autoimmune arthritis, and tumor metastases. This application proposes investigation of the mechanisms by which the interaction between T cells and endothelial cells promotes the enzymatic cleavage and loss of heparan sulfate from cultured endothelial cells and the relationship of this process to T cell activation. The effects of heparan sulfate on the synthesis of cytokines and on the activation and functioning of T cells, macrophages and endothelial cells will be tested in order to deduce its potential contribution to graft rejection.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL046810-01
Application #
3365979
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1991-09-01
Project End
1992-08-31
Budget Start
1991-09-01
Budget End
1992-08-31
Support Year
1
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Type
Schools of Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Xu, Xiulong; Rao, Geetha; Quiros, Roderick M et al. (2007) In vivo and in vitro degradation of heparan sulfate (HS) proteoglycans by HPR1 in pancreatic adenocarcinomas. Loss of cell surface HS suppresses fibroblast growth factor 2-mediated cell signaling and proliferation. J Biol Chem 282:2363-73
Joao, Cristina; Ogle, Brenda M; Geyer, Susan (2006) Immunoglobulin promotes the diversity and the function of T cells. Eur J Immunol 36:1718-28
Cascalho, M; Platt, J L (2006) The future of organ replacement: needs, potential applications, and obstacles to application. Transplant Proc 38:362-4
Quiros, Roderick M; Rao, Geetha; Plate, Janet et al. (2006) Elevated serum heparanase-1 levels in patients with pancreatic carcinoma are associated with poor survival. Cancer 106:532-40
Brunn, Gregory J; Platt, Jeffrey L (2006) The etiology of sepsis: turned inside out. Trends Mol Med 12:10-6
Brunn, Gregory J; Bungum, Marlo K; Johnson, Geoffrey B et al. (2005) Conditional signaling by Toll-like receptor 4. FASEB J 19:872-4
Cascalho, Marilia; Platt, Jeffrey L (2005) New technologies for organ replacement and augmentation. Mayo Clin Proc 80:370-8
Wu, Xiaosheng; Geraldes, Pedro; Platt, Jeffrey L et al. (2005) The double-edged sword of activation-induced cytidine deaminase. J Immunol 174:934-41
Kishore, Sandeep P; Bungum, Marlo K; Platt, Jeffrey L et al. (2005) Selective suppression of Toll-like receptor 4 activation by chemokine receptor 4. FEBS Lett 579:699-704
Johnson, Geoffrey B; Brunn, Gregory J; Samstein, Benjamin et al. (2005) New insight into the pathogenesis of sepsis and the sepsis syndrome. Surgery 137:393-5

Showing the most recent 10 out of 97 publications