Properdin factor D: effects on thrombin-induced platelet aggregation.

Davis, Alvin E.; Kenney, Dianne M.

doi:10.1172/jci109515

Cited by 17 publications

(6 citation statements)

References 30 publications

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“…Platelet a granules also contain factor D, the serine protease that cleaves factor B to its active form. Platelet factor D apparently can inhibit the binding of thrombin to the platelet surface (34). The simultaneous release of factor H may function to inhibit the localized activation of complement by the alternative pathway caused by both the generation of C3b by thrombin (1) as well as high local concentrations of factor D.…”

Section: Discussionmentioning

confidence: 99%

Regulation of the activity of platelet-bound C3 convertase of the alternative pathway of complement by platelet factor H.

Devine¹,

Rosse²

1987

Proc. Natl. Acad. Sci. U.S.A.

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The alternative pathway of complement is regulated on the surface of homologous blood cells at the C3 amplification step by the membrane protein decay-accelerating factor, as well as by the plasma protein factor H. We have reported elsewhere that platelets from patients with paroxysmal nocturnal hemoglobinuria regulate the activity of the C3 convertase C3bBb, even though they lack decay-accelerating factor. We now report that normal human platelets contain factor H, which was released from the platelet in response to complement deposition or thrombin stimulation. Factor H was localized to the platelet at granules by immunocytochemical techniques. As determined by a solid-phase radioimmunoassay, thrombin-stimulated platelets released -54 ng of factor H per 108 platelets. The release of factor H in response to complement or thrombin was inhibited by treating the platelets with metabolic inhibitors. Such inhibition resulted in a 3-fold increase in the activity of C3bBb. Platelets that released factor H bound only half as many molecules of radiolabeled factor B to platelet-bound C3b than platelets that could not release factor H. Treatment of platelets with anti-decay-accelerating factor antibody had no effect on the activity of C3bBb unless the release of factor H was blocked. Therefore, so far as we know, human platelets have a unique mechanism for the regulation of the alternative pathway of complement.

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Section: Discussionmentioning

confidence: 99%

Regulation of the activity of platelet-bound C3 convertase of the alternative pathway of complement by platelet factor H.

Devine¹,

Rosse²

1987

Proc. Natl. Acad. Sci. U.S.A.

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“…TCC, terminal complement complex; MASPs, mannose-binding lectin-associated serine proteases; FD, factor D; FH, factor H; PMPs, platelet microparticles, VWF, von Willebrand factor. factor D, thereby initiating local complement activation (28)(29)(30). As for regulating complement activation, platelets, by secreting Factor H from alpha-granules, either regulate C3 convertase activity or modulate C1q effects via CR3 (31,32).…”

Section: The Effect Of Platelets On Complement Activationmentioning

confidence: 99%

“…As for initiating complement activation, platelet-expressed P- selectin activates complement either on its own or by fixing C3b from spontaneous basal plasmatic C3 cleavage ( 25 – 27 ). Further platelets, by secreting chondroitin sulfate, bind C1q or factor D, thereby initiating local complement activation ( 28 – 30 ). As for regulating complement activation, platelets, by secreting Factor H from alpha-granules, either regulate C3 convertase activity or modulate C1q effects via CR3 ( 31 , 32 ).…”

Section: The Crosstalk Between Complement and Hemostasismentioning

confidence: 99%

“…In homeostatic conditions, the expression of complement regulators CD55 and CD59 on erythrocyte membranes blocks complement activation and protects the erythrocytes from lysis. However, in severe conditions with infection, surgery and autoimmune diseases, intravascular hemolysis caused by the over-activation of TP may occur due to the dysfunction of these two surface-expressed regulators ( 28 , 70 ). Current therapy for IgM-mediated autoimmune hemolytic anemia mainly aims to decrease auto-antibody production.…”

Section: Complement In Hemolytic and Thrombotic Diseasesmentioning

confidence: 99%

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Complement in Hemolysis- and Thrombosis- Related Diseases

Luo

Wang

et al. 2020

Front. Immunol.

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The complement system, originally classified as part of innate immunity, is a tightly self-regulated system consisting of liquid phase, cell surface, and intracellular proteins. In the blood circulation, the complement system, platelets, coagulation system, and fibrinolysis system form a close and complex network. They activate and regulate each other and jointly mediate immune monitoring and tissue homeostasis. The dysregulation of each cascade system results in clinical manifestations and the progression of different diseases, such as sepsis, atypical hemolytic uremic syndrome, C3 glomerulonephritis, systemic lupus erythematosus, or ischemia-reperfusion injury. In this review, we summarize the crosstalk between the complement system, platelets, and coagulation, provide integrative insights into how complement dysfunction leads to hemopathic progression, and further discuss the therapeutic relevance of complement in hemolytic and thrombotic diseases.

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“…Factor D is secreted from platelet a granules after thrombin stimulation and inhibits aggregation of thrombin-activated platelets. 127,128 C3 may be present on human platelets in certain clinical conditions. C3 and immunoglobulins have been detected on the platelets of patients with idiopathic thrombocytopenic purpura, and the interaction with complement has been suggested to promote thrombocytopenia.…”

Section: Platelets and Complementmentioning

confidence: 99%

Platelet Activation in Hemolytic Uremic Syndrome

Karpman

Manea

Vaziri-Sani

et al. 2006

Semin Thromb Hemost

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Platelet consumption in platelet-fibrin aggregates leading to thrombocytopenia and small vessel obstruction are major features of the hemolytic uremic syndrome (HUS). Although thrombocytopenia has been correlated to poor prognosis, the mechanisms by which thrombocytopenia develops in HUS have not been completely elucidated. However, plausible explanations have been platelet contact with thrombogenic surfaces and/or direct contact with an aggregating agent. This article summarizes several mechanisms of platelet activation, interactions with leukocytes, chemokine release, complement activation, and antimicrobial defense. Specific mechanisms are outlined by which platelets may be activated, leading to thrombocytopenia during HUS. In diarrhea-associated HUS Shiga toxin has been shown to injure the endothelium, thus exposing the subendothelium, releasing tissue factor, and rendering the vessel wall prothrombotic. Shiga toxin also binds to and activates platelets. The toxin may activate endothelial cells and platelets simultaneously. In atypical HUS the alternative complement pathway is activated because of mutations in complement regulatory proteins. Mutated factor H does not bind to endothelium and platelets efficiently, enabling complement activation on these cells. In thrombotic thrombocytopenic purpura, intravascular platelet clotting occurs due to dysfunction of the von Willebrand factor (VWF) -cleaving protease ADAMTS13. Thrombi are formed by binding of platelets to ultralarge VWF multimers.

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Properdin factor D: effects on thrombin-induced platelet aggregation.

Cited by 17 publications

References 30 publications

Regulation of the activity of platelet-bound C3 convertase of the alternative pathway of complement by platelet factor H.

Regulation of the activity of platelet-bound C3 convertase of the alternative pathway of complement by platelet factor H.

Complement in Hemolysis- and Thrombosis- Related Diseases

Platelet Activation in Hemolytic Uremic Syndrome

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