| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 278, Issue 11, 9458-9463, March 14, 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Institute for Medicine and Engineering, Department of
Chemical Engineering, University of Pennsylvania, 1010 Vagelos
Research Laboratories, Philadelphia, Pennsylvania 19104
Human neutrophil proteases cathepsin G and
elastase can directly alter platelet function and/or participate in
coagulation cascade reactions on the platelet or neutrophil surface to
enhance fibrin formation. The clotting of recalcified platelet-free
plasma (PFP) or platelet-rich plasma (PRP) supplemented with corn
trypsin inhibitor (to shut down contact activation) was studied in
well-plates or flow assays. Inhibitors of cathepsin G or elastase
significantly delayed the burst time (t50) of
thrombin generation in neutrophil-supplemented PRP from 49 min to 59 and 77 min, respectively, in well-plate assays as well as reduced
neutrophil-promoted fibrin deposition on fibrinogen-adherent platelets
under flow conditions. In flow assays, purified cathepsin G was a far
more potent activator of platelet-dependent coagulation
than elastase. Anti-tissue factor had no effect on neutrophil
protease-enhanced thrombin formation in PRP. The addition of cathepsin
G (425 nM) or convulxin (10 nM) to PRP
dramatically reduced the t50 of thrombin
generation from 53 min to 17 or 23 min, respectively. In contrast, the
addition of elastase to PRP left the t50
unaltered. Whereas perfusion of PFP (
Neutrophil Cathepsin G Promotes Prothrombinase and Fibrin
Formation under Flow Conditions by Activating
Fibrinogen-adherent Platelets*
and
w = 62.5 s
1) over fibrinogen-adherent platelets did not result in
fibrin formation until 50 min, massive fibrin could be observed on
cathepsin G-treated platelets even at 35 min. Cathepsin G addition to
corn trypsin inhibitor-treated PFP produced little thrombin unless anionic phospholipid was present. However, further activation inhibition studies indicated that cathepsin G enhances fibrin deposition under flow conditions by elevating the activation state of
fibrinogen-adherent platelets rather than by cleaving coagulation factors.
*
This study was supported by National Institutes of Health
Grant RO1 HL 56621.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
A National Institutes of Health predoctoral fellow (Grant T32
HL 07954-02).
§
An Established Investigator of the National American Heart
Association. To whom correspondence should be addressed: Institute for
Medicine and Engineering, Dept. of Chemical Engineering, University of
Pennsylvania, 1010 Vagelos Research Laboratories, 3340 Smith Walk,
Philadelphia, PA 19104. Tel.: 215-573-5702; Fax: 215-573-2093; E-mail: sld@seas.upenn.edu.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  K. Ganguly, M. S. Goel, T. Krasik, K. Bdeir, S. L. Diamond, D. B. Cines, V. R. Muzykantov, and J.-C. Murciano Fibrin Affinity of Erythrocyte-Coupled Tissue-Type Plasminogen Activators Endures Hemodynamic Forces and Enhances Fibrinolysis in Vivo J. Pharmacol. Exp. Ther., March 1, 2006; 316(3): 1130 - 1136. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. N. Gosalia, C. M. Salisbury, J. A. Ellman, and S. L. Diamond High Throughput Substrate Specificity Profiling of Serine and Cysteine Proteases Using Solution-phase Fluorogenic Peptide Microarrays Mol. Cell. Proteomics, May 1, 2005; 4(5): 626 - 636. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Nemmar, B. Nemery, P. H. M. Hoet, N. Van Rooijen, and M. F. Hoylaerts Silica Particles Enhance Peripheral Thrombosis: Key Role of Lung Macrophage-Neutrophil Cross-Talk Am. J. Respir. Crit. Care Med., April 15, 2005; 171(8): 872 - 879. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. S. Coller Leukocytosis and Ischemic Vascular Disease Morbidity and Mortality: Is It Time to Intervene? Arterioscler. Thromb. Vasc. Biol., April 1, 2005; 25(4): 658 - 670. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Hafezi-Moghadam, K. L. Thomas, and C. Cornelssen A novel mouse-driven ex vivo flow chamber for the study of leukocyte and platelet function Am J Physiol Cell Physiol, April 1, 2004; 286(4): C876 - C892. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
