Defects in hemostasis in P-selectin-deficient mice

Subramaniam, Meera; Frenette, Paul S.; Saffaripour, Simin; Johnson, Robert C.; Hynes, Richard O.; Wagner, Denisa D.

doi:10.1182/blood.v87.4.1238.bloodjournal8741238

Cited by 191 publications

(86 citation statements)

References 40 publications

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“…P-selectin deficiency may inhibit monocyte trafficking [50] and release of cytokines [51]; however, neutrophils predominate in brain at 24 h after CCI [1,35]. Lack of P-selectin prolongs bleeding time and increases hemorrhage in a local Schwartzman reaction in mice [52]; however, inhibition of P-selectin did not increase central nervous system bleeding in a rat stroke model [53] or after CCI in this study. Other studies suggest a role for P-selectin in neuronal apoptosis and expression of heat shock proteins in ischemic brain [42].…”

Section: Discussionmentioning

confidence: 72%

Reduced brain edema after traumatic brain injury in mice deficient in P-selectin and intercellular adhesion molecule-1

Whalen

Carlos

Dixon

et al. 2000

Journal of Leukocyte Biology

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Platelet (P-) selectin and intercellular adhesion molecule-1 (ICAM-1) mediate accumulation of neutrophils in brain. However, the mechanisms regulating neutrophil accumulation and damage after traumatic brain injury (TBI) are poorly defined. We hypothesized that mice deficient in both P-selectin and ICAM-1 (-/-) would have decreased brain neutrophil accumulation and edema, and improved functional and histopathological outcome after TBI compared with wild-type (+/+). In Protocol I, neutrophils and brain water content were quantified at 24 h after TBI. No difference in brain neutrophil accumulation was observed between groups; however, brain edema was decreased in dual P-selectin and ICAM-1 -/- (P < 0.05 vs. +/+ mice). In Protocol II, after TBI, tests of motor and memory function and histopathology were assessed over 21 days. No difference in motor or memory function or histopathological damage was observed between +/+ and -/- mice. A role for adhesion molecules in the pathogenesis of brain edema independent of leukocyte accumulation in brain is suggested.

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Section: Discussionmentioning

confidence: 72%

Reduced brain edema after traumatic brain injury in mice deficient in P-selectin and intercellular adhesion molecule-1

Whalen

Carlos

Dixon

et al. 2000

Journal of Leukocyte Biology

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“…Third, this model does not include a role for P-selectin. Yet, antibodies to P-selectin inhibit fibrin formation (11), P-selectin null mice have a prolonged bleeding time (39), and thrombi formed in vitro indicate architectural differences when formed from blood of wildtype and P-selectin null mice (40). Using digital videomicroscopy to image the microcirculation of a living mouse, Figure 7.…”

Section: Discussionmentioning

confidence: 99%

Accumulation of Tissue Factor into Developing Thrombi In Vivo Is Dependent upon Microparticle P-Selectin Glycoprotein Ligand 1 and Platelet P-Selectin

Falati

Liu

Gross

et al. 2003

The Journal of Experimental Medicine

694

586

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Using a laser-induced endothelial injury model, we examined thrombus formation in the microcirculation of wild-type and genetically altered mice by real-time in vivo microscopy to analyze this complex physiologic process in a system that includes the vessel wall, the presence of flowing blood, and the absence of anticoagulants. We observe P-selectin expression, tissue factor accumulation, and fibrin generation after platelet localization in the developing thrombus in arterioles of wild-type mice. However, mice lacking P-selectin glycoprotein ligand 1 (PSGL-1) or P-selectin, or wild-type mice infused with blocking P-selectin antibodies, developed platelet thrombi containing minimal tissue factor and fibrin. To explore the delivery of tissue factor into a developing thrombus, we identified monocyte-derived microparticles in human platelet–poor plasma that express tissue factor, PSGL-1, and CD14. Fluorescently labeled mouse microparticles infused into a recipient mouse localized within the developing thrombus, indicating that one pathway for the initiation of blood coagulation in vivo involves the accumulation of tissue factor– and PSGL-1–containing microparticles in the platelet thrombus expressing P-selectin. These monocyte-derived microparticles bind to activated platelets in an interaction mediated by platelet P-selectin and microparticle PSGL-1. We propose that PSGL-1 plays a role in blood coagulation in addition to its known role in leukocyte trafficking.

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“…Activated platelets with surface-exposed P-selectin could associate with and activate previously unactivated platelets, thus providing a mechanism for propagation of platelet thrombi. Failure of this mechanism could explain the mild bleeding diathesis of P-selectin–deficient mice 45 and could contribute to the bleeding tendency in patients with Bernard-Soulier syndrome, the genetic disorder resulting from deficiency of the GP Ib-IX-V complex 46. Nevertheless, this mechanism is likely to be only of secondary importance, as no defect in aggregation has been found in the platelets of patients with Bernard-Soulier syndrome (although a subtle defect might not be detected by conventional methods of performing aggregation).…”

Section: Discussionmentioning

confidence: 99%

The Glycoprotein Ib-IX-V Complex Is a Platelet Counterreceptor for P-Selectin

Romo

Dong

Schade

et al. 1999

The Journal of Experimental Medicine

315

239

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We have identified platelet glycoprotein (GP) Ibα as a counterreceptor for P-selectin. GP Ibα is a component of the GP Ib-IX-V complex, which mediates platelet adhesion to subendothelium at sites of injury. Cells expressing P-selectin adhered to immobilized GP Ibα, and GP Ibα–expressing cells adhered to and rolled on P-selectin and on histamine-stimulated endothelium in a P-selectin–dependent manner. In like manner, platelets rolled on activated endothelium, a phenomenon inhibited by antibodies to both P-selectin and GP Ibα. Unlike the P-selectin interaction with its leukocyte ligand, PSGL-1 (P-selectin glycoprotein ligand 1), the interaction with GP Ibα required neither calcium nor carbohydrate core-2 branching or α(1,3)-fucosylation. The interaction was inhibited by sulfated proteoglycans and by antibodies against GP Ibα, including one directed at a tyrosine-sulfated region of the polypeptide. Thus, the GP Ib-IX-V complex mediates platelet attachment to both subendothelium and activated endothelium.

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Defects in hemostasis in P-selectin-deficient mice

Cited by 191 publications

References 40 publications

Reduced brain edema after traumatic brain injury in mice deficient in P-selectin and intercellular adhesion molecule-1

Reduced brain edema after traumatic brain injury in mice deficient in P-selectin and intercellular adhesion molecule-1

Accumulation of Tissue Factor into Developing Thrombi In Vivo Is Dependent upon Microparticle P-Selectin Glycoprotein Ligand 1 and Platelet P-Selectin

The Glycoprotein Ib-IX-V Complex Is a Platelet Counterreceptor for P-Selectin

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