Hageman Factor regulates inflammatory responses in ARDS

SummaryScavenger phagocytes are mostly responsible for the in vivo clearance of activated or senescent platelets. In contrast to other particulate substrates, the phagocytosis of platelets does not incite pro-inflammatory responses in vivo. This study assessed the contribution of macrophages and dendritic cells (DCs) to the clearance of activated platelets. Furthermore, we verified whether antibodies against the β2 Glycoprotein I (β2GPI), which bind to activated platelets, influence the phenomenon. DCs did not per se internalise activated platelets. In contrast, macrophages efficiently phagocytosed platelets. In agreement with the uneventful nature of the clearance of platelets in vivo, phagocytosing macrophages did not release IL-1β, TNF-α or IL-10. β2GPI bound to activated platelets and was required for their recognition by anti-ββ2GPI antibodies. DCs internalised platelets opsonised by anti-ββ2GPI antibodies. The phagocytosis of opsonised platelets determined the release of TNF-α and IL-1β by DCs and macrophages. Phagocytosing macrophages, but not DCs, secreted the antiinflammatory cytokine IL-1β0. We conclude that anti-ββ2GPI antibodies cause inflammation during platelet clearance and shuttle platelet antigens to antigen presenting DCs.

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Oxidative Stress and Atherosclerosis: Its Relationship to Growth Factors, Thrombus Formation and Therapeutic Approaches

Thrombosis and Haemostasis ◽

10.1055/s-0037-1615550 ◽

1999 ◽

Vol 82 (S 01) ◽

pp. 32-37 ◽

Cited By ~ 22

Author(s):

Karlheinz Peter ◽

Wolfgang Kübler ◽

Johannes Ruef ◽

Thomas K. Nordt ◽

Marschall S. Runge ◽

...

Keyword(s):

Oxidative Stress ◽

Growth Factors ◽

Vessel Wall ◽

Inflammatory Responses ◽

Plaque Rupture ◽

Thrombus Formation ◽

Vascular Lesion ◽

Coagulation System ◽

Therapeutic Approaches ◽

Causative Relationship

SummaryThe initiating event of atherogenesis is thought to be an injury to the vessel wall resulting in endothelial dysfunction. This is followed by key features of atherosclerotic plaque formation such as inflammatory responses, cell proliferation and remodeling of the vasculature, finally leading to vascular lesion formation, plaque rupture, thrombosis and tissue infarction. A causative relationship exists between these events and oxidative stress in the vessel wall. Besides leukocytes, vascular cells are a potent source of oxygen-derived free radicals. Oxidants exert mitogenic effects that are partially mediated through generation of growth factors. Mitogens, on the other hand, are potent stimulators of oxidant generation, indicating a putative self-perpetuating mechanism of atherogenesis. Oxidants influence the balance of the coagulation system towards platelet aggregation and thrombus formation. Therapeutic approaches by means of antioxidants are promising in both experimental and clinical designs. However, additional clinical trials are necessary to assess the role of antioxidants in cardiovascular disease.

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Effects of Ellagic Acid upon the Rabbit Fibrinolytic System

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649010 ◽

1972 ◽

Vol 27 (01) ◽

pp. 063-071

Author(s):

S. G Iatridis ◽

P. G Iatridis

Keyword(s):

Continuous Infusion ◽

Ellagic Acid ◽

Animal Experimentation ◽

Inhibitory Effect ◽

In Vivo Studies ◽

Clot Lysis ◽

Hageman Factor ◽

Lysis Activity ◽

Site Of Action

SummaryThe present investigation deals with in vivo studies of possible relations of active Hageman factor (HFa) to the problems of thrombolysis. The study is based upon animal experimentation in which 40 normal, 5 dicumarolized and 5 heparinized rabbits each received ellagic acid (Elac 10-2 M) by intravenous continuous infusion at a rate of 1 ml/min for a period of 25 min. The data suggest that the Elac infusion induced in vivo activation of HF. Streptokinase (SK) injection 25 min from the start of Elac i. v. infusion failed to induce clot lysis in blood drawn one min after its injection. The phenomenon was more prominent with low (SK 250 U or 500 U) concentrations of SK. With higher concentrations, SK-induced clot lysis activity was not affected by Elac infusion.In dicumarolized and heparinized rabbits Elac infusion still counteracted the fibrinolysis activating effect of low concentration of SK. The possibility that the above described phenomenon was due to either hypercoagulability or to a non-specific inhibitory effect of Elac upon SK was explored and excluded.It is concluded that HFa and SK have the same site of action. Thus it seems that HFa may block the precursor upon which SK acts by forming a complex with it. It is stressed that activation of this precursor by HFa requires a suitable surface.

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The Formation of Intermediate Product I in a Purified System The Role of Factor IX or of its Precursor and of a Hageman Factor-PTA Fraction

Thrombosis and Haemostasis ◽

10.1055/s-0038-1654555 ◽

1961 ◽

Vol 6 (02) ◽

pp. 224-234 ◽

Cited By ~ 4

Author(s):

E. T Yin ◽

F Duckert

Keyword(s):

Intermediate Product ◽

Factor Ix ◽

Assay Method ◽

Lag Phase ◽

Factor X ◽

Haemophilia B ◽

Hageman Factor ◽

One Stage ◽

The One

Summary1. The role of two clot promoting fractions isolated from either plasma or serum is studied in a purified system for the generation of intermediate product I in which the serum is replaced by factor X and the investigated fractions.2. Optimal generation of intermediate product I is possible in the purified system utilizing fractions devoid of factor IX one-stage activity. Prothrombin and thrombin are not necessary in this system.3. The fraction containing factor IX or its precursor, no measurable activity by the one-stage assay method, controls the yield of intermediate product I. No similar fraction can be isolated from haemophilia B plasma or serum.4. The Hageman factor — PTA fraction shortens the lag phase of intermediate product I formation and has no influence on the yield. This fraction can also be prepared from haemophilia B plasma or serum.

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Activation of Hageman Factor by α-Adrenergic Stimulation

Thrombosis and Haemostasis ◽

10.1055/s-0038-1654067 ◽

1970 ◽

Vol 23 (03) ◽

pp. 417-422 ◽

Cited By ~ 13

Author(s):

D. G McKay ◽

J.-G Latour ◽

Mary H. Parrish

Keyword(s):

Disseminated Intravascular Coagulation ◽

Adrenergic Receptor ◽

Adrenergic Stimulation ◽

Hageman Factor ◽

Intravascular Coagulation ◽

Receptor Sites ◽

High Doses ◽

Stimulation Of

SummaryThe infusion of epinephrine in high doses produces disseminated intravascular coagulation by activation of Hageman factor. The effect is blocked by phenoxybenz-amine and is therefore due to stimulation of α-adrenergic receptor sites.

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Consumption of Hageman Factor Activity in the Generalized Shwartzman Reaction Induced by Liquoid

Thrombosis and Haemostasis ◽

10.1055/s-0038-1654150 ◽

1970 ◽

Vol 23 (02) ◽

pp. 386-404 ◽

Cited By ~ 6

Author(s):

G Müller-Berghaus ◽

H. G Lasch

Keyword(s):

Partial Thromboplastin Time ◽

Lethal Dose ◽

Control Group ◽

Factor V ◽

Consumption Coagulopathy ◽

Factor Activity ◽

Hageman Factor ◽

Intravascular Coagulation ◽

Shwartzman Reaction

SummaryThe role of Hageman factor in triggering intravascular coagulation has been studied in rabbits injected intravenously with Liquoid. Besides changes of coagulation parameters characteristic of consumption coagulopathy (e.g. decrease in platelet counts, fibrinogen levels, factor V activity), a pronounced drop in Hageman factor activity was observed after injection of Liquoid. Likewise, the partial thromboplastin time became prolonged.The activation of Hageman factor in vivo could be prevented by intravenous infusion of lysozyme. Twenty min after starting the lysozyme infusion, the partial thromboplastin time became prolonged from a mean of 29 sec to 108 sec. Animals infused with lysozyme and injected with a lethal dose of Liquoid did not develop a consumption coagulopathy. In the same manner, none of 10 animals treated with lysozyme developed the generalized Shwartzman reaction, whereas in the control group 19 out of 20 animals showed fibrin thrombi in the glomerular capillaries.From the present study it may be concluded that the intravascular coagulation process after intravenous injection of Liquoid is triggered by Hageman factor activation.

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