Pretreatment of Human Platelets with Plasmin Inhibits Responses toThrombin, but Potentiates Responses to Low Concentrations of Aggregating Agents, Including the Thrombin Receptor Activating Peptide, SFLLRN

Kinlough-Rathbone, R L; Perry, David S.; Rand, Margaret L.; Packham, MA

doi:10.1055/s-0038-1656044

Cited by 19 publications

(13 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Plasmin has been reported to enzymatically cleave protease-activated receptor-1, a thrombin receptor, 29 and to cause desensitization of biological responses to thrombin. 30 Because plasmin did not cause any contraction by itself in our hands (see Reference 8 for a contrary finding), we are left with the possibility that the augmentation of oxyhemoglobin contractility by plasmin is the result of an elimination of an endogenous thrombin vasorelaxing mechanism that is activated by high concentrations of oxyhemoglobin.…”

Section: Discussionmentioning

confidence: 75%

Thrombin Reduces Cerebral Arterial Contractions Caused by Cerebrospinal Fluid From Patients With Subarachnoid Hemorrhage

Borsody

DeGiovanni

Marton

et al. 2000

Stroke

View full text Add to dashboard Cite

Background and Purpose-We observed that the second application of cerebrospinal fluid (CSF) from subarachnoid hemorrhage (SAH) patients onto cerebral arterial segments in vitro produces a greater contraction than does the initial application. It was hypothesized that the difference between the first and second applications of SAH CSF was due to the activity of thrombin. Methods-Canine vertebrobasilar artery was removed under general anesthesia, cut into rings, and suspended in tissue culture baths so as to measure isometric tension. CSF was taken from patients 1 to 3 days after SAH via ventricular drains. CSF was administered in 10 Ϫ5 to 10 Ϫ1 dilutions. The thrombin antagonist hirudin (5 U) was administered before CSF in some experiments. The arterial tension response to pure oxyhemoglobin (10 Ϫ4 to 3.2 g/dL) and thrombin (10

show abstract

Section: Discussionmentioning

confidence: 75%

Thrombin Reduces Cerebral Arterial Contractions Caused by Cerebrospinal Fluid From Patients With Subarachnoid Hemorrhage

Borsody

DeGiovanni

Marton

et al. 2000

Stroke

View full text Add to dashboard Cite

show abstract

“…Such a cleavage pattern explains the seemingly contradictory earlier data on the effect of plasmin on platelet activation and Ca 2ϩ mobilization, that is, plasmin, at lower concentrations, attenuated thrombin-induced Ca 2ϩ mobilization whereas at high concentrations it activated platelets and caused a modest and gradual increase in cytosolic Ca 2ϩ . 17,[22][23][24][25][26][27] Overall, the general consensus, drawn from the data of published reports, is that plasmin is unlikely to activate PAR-1 in a physiologically significant manner, although it may provide an effective pathway for PAR-1 desensitization in vivo. However, our present data provide convincing evidence that plasmin can effectively induce PAR-1-mediated signaling in vascular fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

Plasmin Induces Cyr61 Gene Expression in Fibroblasts Via Protease-Activated Receptor-1 and p44/42 Mitogen-Activated Protein Kinase–Dependent Signaling Pathway

Pendurthi

Ngyuen

Andrade‐Gordon

et al. 2002

ATVB

View full text Add to dashboard Cite

Objective— The plasminogen system has been proposed to participate in vascular remodeling and angiogenesis. Although plasmin-mediated proteolysis could contribute these processes, proteolytic targets for plasmin and their downstream effector molecules are yet to be fully defined. The aim of the present study was to elucidate potential mechanisms by which plasmin affects various cellular processes. Methods and Results— Plasmin upregulated the expression of Cyr61 , a growth factor–like gene that has been implicated in cell proliferation, adhesion, and migration. Plasmin-induced gene expression is dependent on its proteolytic activity and requires its binding to cells. Studies that used wild-type fibroblasts and fibroblasts derived from PAR-1– and PAR-2–deficient mice showed that plasmin induced Cyr61 gene expression in wild-type fibroblasts and PAR-2–deficient cells but not in PAR-1–deficient cells. Consistent with this, plasmin induced the activation of p44/42 mitogen-activated protein kinase in wild-type, PAR-2 −/− cells but not in PAR-1 −/− cells. In contrast with thrombin, plasmin failed to induce Ca 2+ signaling in fibroblasts. Conclusions— Plasmin induced an angiogenic and wound-healing promoter, Cyr61, in fibroblasts through activation of PAR-1. Plasmin-induced Cyr61 expression is mediated via the p44/42 mitogen-activated protein kinase pathway independent of Ca 2+ signaling.

show abstract

“…The method is described in detail elsewhere [13]. Washed human platelets were labeled with 14 C-serotonin, treated for 30 min at 378C with the two aforementioned concentrations of aspirin, washed and re-suspended in a Tyrode-albumin solution with apyrase (4 U/ml) (Grade VI; Sigma-Aldrich, St Louis, Missouri, USA).…”

Section: Inhibition Of Platelet Signaling With Apyrasementioning

confidence: 99%

Aspirin inhibits surface glycoprotein IIb/IIIa, P-selectin, CD63, and CD107a receptor expression on human platelets

McKenzie

Malinin

Bell

et al. 2003

Blood Coagulation & Fibrinolysis

View full text Add to dashboard Cite

Platelet inhibition after aspirin therapy reduces the risk for the development of acute coronary syndromes. However, the mechanism by which aspirin affect platelets other than by prostaglandin blockade is unclear. We sought to determine the in vitro effects of aspirin on the surface expression of nine platelet receptors using whole blood flow cytometry. Blood from 24 healthy volunteers was incubated for 30 min with 1.8 and 7.2 mg/l phosphate-buffered saline-diluted acetylsalicylic acid in the presence or absence of apyrase. Platelet serotonin release, and the surface expression of platelet receptors with or without apyrase were determined using the following monoclonal antibodies: anit-CD41 [glycoprotein (GP)IIb/IIIa], CD42b (GPIb), CD62p (P-selectin), CD51/CD61 (vitronectin receptor), CD31 [platelet/endothelial cellular adhesion molecule-1 (PECAM-1)], CD107a [lysosomal associated membrane protein (LAMP)-1], CD107b (LAMP-2), CD63 (LIMP or LAMP-3), and CD151 (PETA-3). Samples were then immediately fixed with 2% paraformaldehyde, and run on the flow cytometer within 48 h. Aspirin does not affect serotonin release from human platelets. Dose-dependent inhibition of GPIIb/IIIa, P-selectin, CD63, and CD107a receptor expression was observed in the aspirin-treated whole-blood samples. Apyrase potentiates the effects of aspirin, and independently inhibits PECAM-1. In addition to the known effect of irreversibly inhibiting platelet cyclooxygenase-1, thereby blocking thromboxane A(2) synthesis, it appears that aspirin exhibits direct effects on selective major platelet receptors.

show abstract

Pretreatment of Human Platelets with Plasmin Inhibits Responses toThrombin, but Potentiates Responses to Low Concentrations of Aggregating Agents, Including the Thrombin Receptor Activating Peptide, SFLLRN

Cited by 19 publications

References 35 publications

Thrombin Reduces Cerebral Arterial Contractions Caused by Cerebrospinal Fluid From Patients With Subarachnoid Hemorrhage

Thrombin Reduces Cerebral Arterial Contractions Caused by Cerebrospinal Fluid From Patients With Subarachnoid Hemorrhage

Plasmin Induces Cyr61 Gene Expression in Fibroblasts Via Protease-Activated Receptor-1 and p44/42 Mitogen-Activated Protein Kinase–Dependent Signaling Pathway

Aspirin inhibits surface glycoprotein IIb/IIIa, P-selectin, CD63, and CD107a receptor expression on human platelets

Contact Info

Product

Resources

About