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Faculty James O'Rourke
Professor of Immunology
jorourke@uchc.edu
Areas of Interest:
We are investigating the production of extravascular tissue
plasminogen activator (t-PA) by sympathetic neurons, and its effects on
the blood and vessel wall fibrinolysis. Plasmin, formed by the action of
t-PA on plasminogen, is the master enzyme of fibrinolysis and
extracellular matrix remodeling. Extravascular plasmin produced by t-PA
is able to degrade most proteins, and is a principal activator of latent
metalloproteinases that also degrade the matrix. In various
immunological reactions, plasmin is a principal activator of important
cytokines, such as TGF-b which regulates numerous immune and healing
reactions. As such plasmin production plays a major role in the
pathogenesis of vessel wall diseases, e.g., hypertension,
atherosclerosis and thromboembolism.
Within most tissues and organs the vascular endothelial cell is
thought to be the principal source of tissue plasminogen activator. Our
studies have confirmed that greater amounts of the protease are
synthesized, transported and released by sympathetic nerve cells that
innervate the vessel walls and other extracellular matrices throughout
the body. This indicates that t-PA is distributed by the sympathetic
nervous system to multiple tissues and organs. The implications of this
neural fibrinolysis for diseases of ageing are studied in appropriate
animal models using invitro t-PA release measurements in organ cultures
and morphologic TEM studies of t-PA distribution.
Publications
Selected Publications:
Wang, Y. Ghalil, W. Pingle, P., Traboulsi, A. Dalal, T. O'Rourke, J.
and Cone, R.E. Splenic cells from mice receiving intracameral antigen
suppress in vitro antigen‑induced proliferation and interferon‑g
production by sensitized lymph node cells. Ocular Immunol and Inflam.,
(In press).
Jiang, X., Hand, A.R., Shen, S., Cone, R.E. and O'Rourke, J. Enhanced
tissue plasminogen activator synthesis by the sympathetic neurons that
innervate aging vessels. J. Neurosci Res. 71:567‑594, 2003.
Wang, Y., Jiang, X., Hand, A.R., Gillies, C., Kirk, J., Gone, R.E.,
and O'Rourke, J. Additional evidence that the sympathetic nervous system
regulates the vessel wall release of tissue plasminogen activator. Blood
Coag. and Fibrinolysis 13:1‑11, 2002.
Jiang, X., Wang, Y., Hand, A_R., Gillies, C., Cone, R.E. Kirk, J.,
and O'Rourke, J. Storage and release of tissue plasminogen activator
(t‑PA) by sympathetic axons in resistance vessel walls. Microvascular
Research 64:438‑447, 2002.
Wang, Y., Goldschneider, I., O'Rourke, J. and Cone, R.E. Blood
mononuclear cells induce regulatory NK T lymphocytes in anterior
chamber‑associated immune deviation. J. Leukocyte Biol. 69:741‑746,
2001.
Jiang, X, Wang, Y., Hand, A.R., Gillies, C., and O'Rourke, J.
Presence of tissue plasminogen activator (t‑PA) in the adventitial
sympathetic nerves that innervate small arteries: Morphologic evidence
for a neural fibrinolysis. Fibrinolysis and Proteolysis 14:35‑46, 2000.
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