Inhibition of the activation of Hageman factor (factor XII) by human vascular endothelial cell culture supernates.

Ratnoff, Oscar D.; Everson, Barbara; Embury, Paula; Ziats, Nicholas P.; Anderson, James M.; Emanuelson, Marlene M.; Malemud, Charles J.

doi:10.1073/pnas.88.23.10740

Cited by 9 publications

(5 citation statements)

References 15 publications

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“…These data suggest that FXII auto-activation is not a physiologic phenomenum. The lack of FXII activation following incubation on HUVEC may be due to a HUVEC secreted substance reported to inhibit FXII activation on artificial negatively charged surfaces (29,30). This unidentified substance may be identical to the agent reported to inhibit FXII activation by ellagic acid in the presence of a suspension of peripheral blood mononuclear cells, monocytes, T or B lymphocytes, platelets, granulocytes, eosinophils or celldepleted supernatant fluids of these suspensions (31,32).…”

Section: Discussionmentioning

confidence: 92%

Factor XII Does not Initiate Prekallikrein Activation on Endothelial Cells

Røjkjær¹,

Hasan²,

Motta³

et al. 1998

Thromb Haemost

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SummaryIt is well known that on artificial surfaces, binding and autoactivation of factor XII (FXII) is the initiating event of plasma prekallikrein (PK) activation. We performed investigations to examine whether this mechanism was true for FXII activation on endothelial cells (HUVEC). Activation of PK on HUVEC required an optimal substrate and Zn2+ concentration, the latter of which varied with the buffer’s carrier protein. Maximal PK activation required the addition of 250 μM or 10 μM Zn2+ to buffers containing bovine serum albumin (BSA) or gelatin, respectively. However, the actual free Zn2+ concentration in these buffers was the same at 8 μM. In both BSA- and gelatin-containing buffers and using two different chromogenic substrates for FXII, no autoactivation of FXII on HUVEC was seen when incubated for up to 60 min. Rather, initiation of FXII enzymatic activity required the presence of PK. FXII activation after PK activation contributed to the extent of measured enzymatic activity, but its role was secondary because treatment with corn trypsin inhibitor or a neutralizing antibody to FXIIa did not abolish the measured enzymatic activity. They also reduced the activity to the level seen with PK activation alone. Alternatively, soybean trypsin inhibitor abolished the proteolytic activity associated with PK and FXII activation on HUVEC. Further, only normal human and FXII-deficient plasmas, not PK-deficient plasma, had the ability to generate proteolytic activity when incubated over endothelial cells. In a purified system, maximal PK activation was measured after a 10-15 min incubation depending upon the concentration of reactants. When FXII was added with the PK, maximal activation occurred within 7.5-10 min. In normal human or FXII-deficient plasmas, but not in PK-deficient plasma, maximal activation was seen in 4 min. These data indicate that on HUVEC, unlike artificial surfaces, PK activation when bound to HK is the initiating activation event in this system. FXII activation is secondary to PK activation and contributes to the extent of measured enzymatic activity. These data challenge the accepted dogmas of “contact activation” and suggest that on biologic membranes a new notion as to how this system is activated needs to be considered.

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Section: Discussionmentioning

confidence: 92%

Factor XII Does not Initiate Prekallikrein Activation on Endothelial Cells

Røjkjær¹,

Hasan²,

Motta³

et al. 1998

Thromb Haemost

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“…Moreover, it has been demonstrated that factor XI1 bound to endothelial cells may become gradually autoactivated during a two hour interval (244). However, other studies have shown that both conditioned medium and lysates of human umbilical vein endothelial cells contain substances that impair the formation of factor XIIa when activated by different active surfaces (245,246). Partial purification of the inhibitory fraction from the cell lysates has revealed a protein of 22.5 kDa, which was different from other intrinsic coagulation inhibitors (246).…”

Section: Endotheli~irn and Factor XIImentioning

confidence: 91%

Anticoagulant Properties of the Vascular Endothelium

1997

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“…Inhibitory activity has also been found in normal human plasma [ 161, and in several plasma constituents, including the C Iq subcomponent of the first component of complement (C 1) [ 171, and P,-glycoprotein I [ 18,191, Platelet factor 4, too, inhibits activation of Hageman factor [20][21][22], These observations raise the possibility that these and similar agents may foster the fluidity of blood by interfering with initiation of the intrinsic pathway of thrombin formation. One or more such substances have been detected in the supernatant fluid of cultured human vascular endothelial cells, suggesting that these agents may have relevance to the prevention of inadvertent intravascular clotting [23].…”

Section: Discussionmentioning

confidence: 97%

Inhibition of the activation of hageman factor (factor XII) by eosinophils and eosinophilic constituents

et al. 1993

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Several syndromes characterized by striking eosinophilia may be complicated by thrombosis. The experiments described indicate that, paradoxically, eosinophils and certain of their constituents inhibit the activation of Hageman factor (HF, factor XII). In earlier studies, suspensions of mixed types of granulocytes, other nucleated peripheral blood cells, and platelets inhibited activation of Hageman factor by ellagic acid, glass, and sulfatides. After these cells were sedimented by centrifugation, the supernatant fluids were also inhibitory. No attempt had been made earlier to distinguish among different granulocytic species. In the present study, suspensions of eosinophils and the supernatant fluid after eosinophils had been separated by centrifugation inhibited activation of Hageman factor by ellagic acid. The protein concentration of that amount of supernatant fluid that inhibited activation by about half was 16 micrograms/ml, approximately the same as had been described for suspensions of peripheral blood mononuclear cells. Activation of Hageman factor by ellagic acid was also inhibited by certain constituents of eosinophils, including eosinophil peroxidase, eosinophil major basic protein and eosinophil cationic protein. Inhibition was not specific for ellagic acid-induced activation of Hageman factor, as inhibition was also observed with sulfatide-induced activation. Inhibition was presumably related to neutralization of the negative charge of activators of Hageman factor. Thus, bismuth subgallate, a particulate activator of Hageman factor, was no longer effective after it had been exposed to eosinophil cationic protein. The observations reported here raise the question of whether in vivo eosinophils modulate certain of the defense reactions ascribed to Hageman factor.

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Inhibition of the activation of Hageman factor (factor XII) by human vascular endothelial cell culture supernates.

Cited by 9 publications

References 15 publications

Factor XII Does not Initiate Prekallikrein Activation on Endothelial Cells

Factor XII Does not Initiate Prekallikrein Activation on Endothelial Cells

Anticoagulant Properties of the Vascular Endothelium

Inhibition of the activation of hageman factor (factor XII) by eosinophils and eosinophilic constituents

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