| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Medical Care Line, Michael E. DeBakey V.A. Medical Center, Houston, TX, USA; Medicine, Baylor College of Medicine, Houston, TX, USA; Pediatrics, Baylor College of Medicine, Houston, TX, USA
2 Pediatrics, Baylor College of Medicine, Houston, TX, USA
3 Medicine, Baylor College of Medicine, Houston, TX, USA
4 Pathology, Baylor College of Medicine, Houston, TX, USA
5 Medicine, Baylor College of Medicine, Houston, TX, USA; Pediatrics, Baylor College of Medicine, Houston, TX, USA
* To whom correspondence should be addressed. E-mail: rrumbaut{at}bcm.tmc.edu.
Endotoxemia promotes adhesive interactions between platelets and microvascular endothelium in vivo. We sought to determine whether endotoxin (LPS) modified platelet thrombus formation in mouse cremaster venules, and whether Toll-like receptor 4 (TLR4) and neutrophils were involved in the response. Intravital videomicroscopy was performed in the cremaster microcirculation of pentobarbital-anesthetized mice; venular platelet thrombi were induced with a light/dye endothelial injury model. C57BL/6 mice treated with E. coli endotoxin had enhanced rates of venular platelet thrombus formation: the time to microvessel occlusion was reduced by ~50% (p < 0.005) compared to saline-treated animals. Enhanced microvascular thrombosis was evident as early as two hours following LPS administration. LPS had no effect on thrombosis in either of two mouse strains with altered TLR4 signaling (C57BL/10ScNJ or C3H/HeJ), whereas it enhanced thrombosis in the control strains (C57BL/10J and C3H/HeN). LPS also enhanced platelet adhesion to endothelium in the absence of light/dye injury. Platelet adhesion, but not enhanced thrombosis, was inhibited by depletion of circulating neutrophils. LPS failed to enhance platelet aggregation ex vivo, and did not influence platelet P-selectin expression, a marker of platelet activation. These findings support the notion that endotoxemia promotes platelet thrombus formation independent of neutrophils, and without enhancement of platelet aggregation, via a TLR4-dependent mechanism.
This article has been cited by other articles:
|
|
 |
|
  T.-T. Hong, J. Huang, T. D. Barrett, and B. R. Lucchesi Effects of cyclooxygenase inhibition on canine coronary artery blood flow and thrombosis Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H145 - H155. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Anthoni, J. Russell, K. C. Wood, K. Y. Stokes, T. Vowinkel, D. Kirchhofer, and D. N. Granger Tissue factor: a mediator of inflammatory cell recruitment, tissue injury, and thrombus formation in experimental colitis J. Exp. Med., July 9, 2007; 204(7): 1595 - 1601. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.-l. Stahl, M. Svensson, M. Morgelin, C. Svanborg, P. I. Tarr, J. C. Mooney, S. L. Watkins, R. Johnson, and D. Karpman Lipopolysaccharide from enterohemorrhagic Escherichia coli binds to platelets through TLR4 and CD62 and is detected on circulating platelets in patients with hemolytic uremic syndrome Blood, July 1, 2006; 108(1): 167 - 176. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
