IJNN :: IJNN Volume 2 :: Volume 2 - Issue 1 - October 2005 :: Volume 2 - Issue 1 - Reviews :: Vol 2 - Iss 1 - Review - Blood-derived proteases and inflammatory processes in the brain: Is thrombin involved in microglial cytokine release?


	Home


	Shopping Cart


	Contact Us


	Article Submission


	GCNPNR.org

All Enquiries: +44 (0)20 8487 1421 Mobile: +44 (0)7878 201 416

Search:

Advanced search

Printable version

Categories

Information

Contact us
Privacy statement
Terms & Conditions
Scope of Journal
Editorial Board
Reprints Order Form
Advertise in the IJNN
Sponsored Supplements
Company Info

IJNN :: IJNN Volume 2 :: Volume 2 - Issue 1 - October 2005 :: Volume 2 - Issue 1 - Reviews :: Vol 2 - Iss 1 - Review - Blood-derived proteases and inflammatory processes in the brain: Is thrombin involved in microglial cytokine release?

Vol 2 - Iss 1 - Review - Blood-derived proteases and inflammatory processes in the brain: Is thrombin involved in microglial cytokine release? #16237

Blood-derived proteases and inflammatory processes in the brain:
Is thrombin involved in microglial cytokine release?

Uwe-Karsten Hanisch1, Denise van Rossum1, Jonathan Weinstein2 and Thomas Möller2

1Institute of Neuropathology, University of Göttingen
2Department of Neurology, University of Washington, Seattle

Received 15 March 2005; accepted 25 September 2005

Correspondence and requests for reprints should be addressed to:
Dr. Uwe-Karsten Hanisch
University of Göttingen
Institute of Neuropathology
Robert-Koch-Straße 40
D-37075 Göttingen
Germany
Tel: +49-551-396520
Fax: +49-551-398472
E-Mail: ukhanisch@med.uni-goettingen.de

Abstract
Upon blood-brain barrier disruption, serum components may develop a tremendous impact on glial and neuronal cells. We have focussed on thrombin, a blood-derived serine protease and major coagulation factor, as to its ability to trigger functional responses in microglia, the macrophage equivalent of the central nervous system. These cells express proteinase-activated receptors (PAR) for thrombin. Activated by partial proteolysis, PAR trigger cytosolic consequences, thus serving signal transduction processes of certain proteases. Accordingly, microglial PAR should also mediate the induction of cytokines and chemokines, a function recently assigned to thrombin. Here, however, we discuss findings that may force a revision of this notion. Inhibition of the proteolytic activity as well as interference with substrate/receptor binding of thrombin had no effect on the induction of microglial cyto- and chemokine release. Moreover, a direct stimulation of microglial PAR by synthetic ligands failed to induce any release response. Biochemical analysis rather revealed a distinct fraction of associated protein as the sole carrier of the induction activity. As a conclusion, thrombin proper is apparently not able to trigger the microglial release activity. This observation could also impact on other cellular functions previously reported for preparations of thrombin and other proteases. However, expression of PAR and the demonstration of true responses to -thrombin in vitro indicate that microglia remains a target of thrombin actions in the CNS.

Key words

Microglia, neuroinflammation, proteases, thrombin

Details

Price: €25.00

Options

Quantity

Add to cart

Send to friend

Your name: *

Your e-mail: *

Recipient's e-mail: *

Send to friend

Your cart

	Cart is empty

View cart
Checkout

Authentication

Username

Password

Recover password

If Javascript is disabled in your browser click here