|
|
|
|
|
|
|
|
|||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | |||||
Journal of Cell Science, Vol 112, Issue 22 4007-4016, Copyright © 1999 by Company of Biologists
JOURNAL ARTICLES |
AD Rogove, C Siao, B Keyt, S Strickland and SE Tsirka
Program in Pharmacology, MSTP Program, Department of Psychiatry, University Medical Center at Stony Brook, Stony Brook, NY 11794-8101, USA.
Tissue plasminogen activator mediates excitotoxin-induced neurodegeneration and microglial activation in the mouse hippocampus. Here we show that tissue plasminogen activator (tPA) acts in a protease-independent manner to modulate the activation of microglia, the cells of the central nervous system with macrophage properties. Cultured microglia from tPA-deficient mice can phagocytose as efficiently as wild-type microglia. However, tPA-deficient microglia in mixed cortical cultures exhibit attenuated activation in response to lipopolysaccharide, as judged by morphological changes, increased expression of the activation marker F4/80 and the release of the pro-inflammatory cytokine tumor necrosis factor-(&agr;). When tPA is added to tPA deficient cortical cultures prior to endotoxin stimulation, microglial activation is restored to levels comparable to that observed in wild-type cells. Proteolytically-inactive tPA can also restore activation of tPA-deficient microglia in culture and in vivo. However, this inactive enzyme does not restore susceptibility of tPA-deficient hippocampal neurons to excitotoxin-mediated cell death. These results dissociate two different functions of tPA: inactive enzyme can mediate microglial activation, whereas proteolytically-competent protein also promotes neuronal degeneration. Thus tPA is identified as a new cytokine in the central nervous system.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  A. L. Samson, R. J. Borg, B. Niego, C. H. Y. Wong, P. J. Crack, T. Yongqing, and R. L. Medcalf A nonfibrin macromolecular cofactor for tPA-mediated plasmin generation following cellular injury Blood, August 27, 2009; 114(9): 1937 - 1946. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Zhang, J. An, D. K. Strickland, and M. Yepes The Low-Density Lipoprotein Receptor-Related Protein 1 Mediates Tissue-Type Plasminogen Activator-Induced Microglial Activation in the Ischemic Brain Am. J. Pathol., February 1, 2009; 174(2): 586 - 594. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Wang and S. Dore Heme oxygenase-1 exacerbates early brain injury after intracerebral haemorrhage Brain, June 1, 2007; 130(6): 1643 - 1652. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Sheehan, C. Zhou, I. Gravanis, A. D. Rogove, Y.-P. Wu, D. F. Bogenhagen, and S. E. Tsirka Proteolytic Activation of Monocyte Chemoattractant Protein-1 by Plasmin Underlies Excitotoxic Neurodegeneration in Mice J. Neurosci., February 14, 2007; 27(7): 1738 - 1745. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Parathath, S. Parathath, and S. E. Tsirka Nitric oxide mediates neurodegeneration and breakdown of the blood-brain barrier in tPA-dependent excitotoxic injury in mice J. Cell Sci., January 15, 2006; 119(2): 339 - 349. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. Mali, M. Cheng, and S. K. Chintala Plasminogen activators promote excitotoxicity-induced retinal damage FASEB J, August 1, 2005; 19(10): 1280 - 1289. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Nicole, A. Goldshmidt, C. E. Hamill, S. D. Sorensen, A. Sastre, P. Lyuboslavsky, J. R. Hepler, R. J. McKeon, and S. F. Traynelis Activation of Protease-Activated Receptor-1 Triggers Astrogliosis after Brain Injury J. Neurosci., April 27, 2005; 25(17): 4319 - 4329. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Wang and S. E. Tsirka Tuftsin Fragment 1-3 Is Beneficial When Delivered After the Induction of Intracerebral Hemorrhage Stroke, March 1, 2005; 36(3): 613 - 618. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Brownstein, A. B. Deora, A. T. Jacovina, R. Weintraub, M. Gertler, K. M. F. Khan, D. J. Falcone, and K. A. Hajjar Annexin II mediates plasminogen-dependent matrix invasion by human monocytes: enhanced expression by macrophages Blood, January 1, 2004; 103(1): 317 - 324. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-J. Siao, S. R. Fernandez, and S. E. Tsirka Cell Type-Specific Roles for Tissue Plasminogen Activator Released by Neurons or Microglia after Excitotoxic Injury J. Neurosci., April 15, 2003; 23(8): 3234 - 3242. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. T. Liberatore, A. Samson, C. Bladin, W.-D. Schleuning, and R. L. Medcalf Vampire Bat Salivary Plasminogen Activator (Desmoteplase): A Unique Fibrinolytic Enzyme That Does Not Promote Neurodegeneration Stroke, February 1, 2003; 34(2): 537 - 543. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Lu, M. Bhasin, and S. E. Tsirka Involvement of Tissue Plasminogen Activator in Onset and Effector Phases of Experimental Allergic Encephalomyelitis J. Neurosci., December 15, 2002; 22(24): 10781 - 10789. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Wyllie, P. Seu, F. Q. Gao, P. Gros, and J. A. Goss Disruption of the Nramp1 (also known as Slc11a1) gene in Kupffer cells attenuates early-phase, warm ischemia-reperfusion injury in the mouse liver J. Leukoc. Biol., November 1, 2002; 72(5): 885 - 897. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-J. Siao and S. E. Tsirka Tissue Plasminogen Activator Mediates Microglial Activation via Its Finger Domain through Annexin II J. Neurosci., May 1, 2002; 22(9): 3352 - 3358. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Gveric, R. Hanemaaijer, J. Newcombe, N. A. van Lent, C. F. M. Sier, and M. L. Cuzner Plasminogen activators in multiple sclerosis lesions: Implications for the inflammatory response and axonal damage Brain, October 1, 2001; 124(10): 1978 - 1988. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Brodsky, J. Chen, A. Lee, K. Akassoglou, J. Norman, and M. S. Goligorsky Plasmin-dependent and -independent effects of plasminogen activators and inhibitor-1 on ex vivo angiogenesis Am J Physiol Heart Circ Physiol, October 1, 2001; 281(4): H1784 - H1792. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Davies, I. R. Kearns, J. Ure, C. H. Davies, and R. Lathe Loss of Hippocampal Serine Protease BSP1/Neuropsin Predisposes to Global Seizure Activity J. Neurosci., September 15, 2001; 21(18): 6993 - 7000. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Ahmed, D. Gveric, G. Pryce, D. Baker, J. P. Leonard, and M. L. Cuzner Myelin/Axonal Pathology in Interleukin-12 Induced Serial Relapses of Experimental Allergic Encephalomyelitis in the Lewis Rat Am. J. Pathol., June 1, 2001; 158(6): 2127 - 2138. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Akassoglou, K. W. Kombrinck, J. L. Degen, and S. Strickland Tissue Plasminogen Activator-Mediated Fibrinolysis Protects against Axonal Degeneration and Demyelination after Sciatic Nerve Injury J. Cell Biol., May 29, 2000; 149(5): 1157 - 1166. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. P. Wu, C.-J. Siao, W. Lu, T.-C. Sung, M. A. Frohman, P. Milev, T. H. Bugge, J. L. Degen, J. M. Levine, R. U. Margolis, et al. The Tissue Plasminogen Activator (Tpa/Plasmin) Extracellular Proteolytic System Regulates Seizure-Induced Hippocampal Mossy Fiber Outgrowth through a Proteoglycan Substrate J. Cell Biol., March 20, 2000; 148(6): 1295 - 1304. [Abstract] [Full Text] [PDF]
|
|
