Activation of Rabbit Hageman Factor by Homogenates of Cultured Rabbit Endothelial Cells

Wiggins, Roger C.; Loskutoff, David J.; Cochrane, Charles G.; Griffin, John H.; Edgington, Thomas S.

doi:10.1172/jci109651

Cited by 75 publications

(23 citation statements)

References 34 publications

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“…However, we reasoned that since sustained external balloon compression of the MCA may produce focal (e.g., ischemic) endothelial disruption, the coagulation cascade may be activated locally through both extrinsic (via tissue thromboplastin and Factor VII) and intrinsic (via Factor XII) pathways. 36 ' 37 In association with consequent prolonged complete stasis, as produced experimentally in the end-arterioles of the affected corpus striatum, sufficient thrombin may be generated to form occluding thrombus. In the absence of complete stasis, as in the MCA, thrombin generation would be insufficient for thrombus formation.…”

Section: Discussionmentioning

confidence: 99%

Experimental acute thrombotic stroke in baboons.

Zoppo¹,

Copeland²,

Harker³

et al. 1986

Stroke

157

138

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SUMMARY To study the effects of antithrombotic therapy in experimental stroke, we have characterized a baboon model of acute cerebrovascular thrombosis. In this model an inflatable silastic balloon cuff has been implanted by transorbital approach around the right middle cerebral artery (MCA), proximal to the take-off of the lentlculostriate arteries (LSA). Inflation of the balloon for 3 hours in six animals produced a stereotypic sustained stroke syndrome characterized by contralateral hemiparesis. An Infarction volume of 3.2 ± 1 . 5 cm 3 in the ipsilateral corpus striatum was documented by computerized tomographic (CT) scanning at 10 days following stroke induction and 3.9 ± 1 . 9 cm 3 (n = 4) at 14 days by morphometric Deuropathotogic determinations of brain specimens fixed in situ by pressure-perfusion with 10% buffered formalin.Immediate pressure-perfusion fixation following deflation of the balloon was performed in 16 additional animals given Evans blue dye intravenously prior to the 3 hour MCA balloon occlusion. Light microscopy and transmission electron microscopy consistently confirmed the presence of thrombotic material occluding microcirculatory branches of the right LSA in the region of Evans blue stain, but not those of the contralateral corpus striatum.When autologous '"in-platelets were infused intravenously in four animals from the above group prior to the transient 3 hour occlusion of the right MCA, gamma scintillation camera imaging of each perfused-flxed whole brain demonstrated the presence of a single residual focus of '"in-platelet activity involving only the Evans blue-stained right corpus striatum. Focal right hemispheric activity was equivalent to 0.55 ± 0.49 ml of whole blood, and the occlusion score derived from histologic examination of the microcirculatton of the Evans blue-stained corpus striatum averaged 34.8 ± 2.8. Similar "'in-platelct imaging and histologic scoring experiments carried out hi four animals pretreated with the antithrombotic combination heparin and tidopidine showed marked reduction of both "'in-platelet activity (0.01 ± 0.03 ml vs. 0.55 ± 0.49 ml; p < 0.01) and thrombotic occlusion of the microcirculation (10.8 ± 7.4 units vs. 34.8 ± 2.8 units; p < 0.01) in the right corpus striatum following 3 hours of MCA occlusion. In separate control experiments "'inlabeled autologous platelets were infused after the 3 hour period of right MCA occlusion and subsequent balloon deflation hi two animals; no focus of '"in-platelet activity was demonstrated in fixed whole brain.We conclude that thrombi form in situ In the microcirculation of perforating branches of the LSA located in the ipsilateral corpus striatum following a 3 hour period of MCA occlusion and that these thrombi may be prevented when antithrombotic therapy is administered prior to MCA balloon occlusion. This model of acute thrombotic stroke may be useful to assess the safety and efficacy of thrombolytic therapies.

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Section: Discussionmentioning

confidence: 99%

Experimental acute thrombotic stroke in baboons.

Zoppo¹,

Copeland²,

Harker³

et al. 1986

Stroke

157

138

View full text Add to dashboard Cite

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“…HFa has recently been found to increase cutaneous vascular permeability in quantities as low as 3 ng, i.e., 1/10,000th the amount of HF present in 1 ml of plasma.2 In vitro studies of the system have demonstrated that negatively charged substances may activate the system. Vascular basement membrane (13) and collagen preparations (14,16), bacterial lipopolysaccharides (17), and serine protease(s) released from cultured endothelial cells (18), are capable of cleaving and activating the system. Thus through activation of complement, contact (HF), and clotting systems of plasma a number of effector agents are generated that could mediate many of the pathologic features of ARDS.…”

Section: Introductionmentioning

confidence: 99%

Studies on the Pathogenesis of the Adult Respiratory Distress Syndrome

Mcguire¹,

Spragg²,

Cohen³

et al. 1982

J. Clin. Invest.

Self Cite

315

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AB S T R A C T Bronchoalveolar lavage (BAL) fluid was obtained from 24 sequentially studied patients with adult respiratory distress syndrome (ARDS) for assessment of potential activating and mediating factors. Proteolytic activity of the fluids was observed by measuring cleavage of radiolabeled proteins of the contact (Hageman factor) and complement systems. Proteolytic activity was observed in 17 of 24 (71%) patients with ARDS, and BAL fluid of the 7 ARDS patients without demonstrable, active, enzyme exhibited inhibitory activity for the proteolytic activity. The enzymes cleaved Hageman factor, prekallikrein, plasminogen, high molecular weight kininogen, C4, C3, C5, and Factor B of the complement system. Cleavage of the contact system proteins producted fragments similar or identical in size to the fragments observed during activation of these molecules, although continued incubation invariably reduced the protein to small peptide fragments. None of 7 normal individuals, and 29 of 99 patients (29%) with other forms of pulmonary disease contained measurable enzymes.The proteolytic activity in BAL fluid of ARDS patients was blocked by diisopropylphosphofluoridate (0.1 mM), Trasylol, soybean trypsin inhibitor, and normal plasma, or plasma deficient in inhibition of the first component of complement. hibitor (al-Pl)-deficient plasma failed to inhibit the proteolytic activity and addition of al-PI to the deficient plasma reconstituted the inhibition.Much of the proteolytic activity of the BAL fluid from ARDS patients was identified as neutrophil elastase: the fluids cleaved elastin and synthetic peptide Dr. McGuire is a recipient of a Parker B. Francis Foundation fellowship.

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“…Activation of HF can be brought about by its exposure to negatively charged agents such as glass, kaolin (22), ellagic acid (33), a serine protease that is present in the microsomal fraction of endothelial cells (34), a combination of collagen and some other unidentified basement membrane components (27), and some but not all preparations of collagen (5)(6)(7)(8)(9)(10)(11)(12)(13). HF that has been activated during the "contact phase" of blood coagulation is inhibited by CI inactivator (35) and antithrombin III (36).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of the activation of Hageman factor (factor XII) by complement subcomponent C1q.

Rehmus¹,

Greene²,

Everson³

et al. 1987

J. Clin. Invest.

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MethodsHageman factor (HF, Factor XII) is activated by glass, collagen, and ellagic acid, and initiates blood coagulation via the intrinsic pathway. Clq inhibits collagen-induced platelet aggregation and adherence of platelets to glass, effects attributable to the collagenlike region of Clq. We examined the actions of Clq on HF activation. Incubation of Clq with HF before addition of HF-deficient plasma extended the activated partial thromboplastin time.Similarly, when glass tubes were coated with Clq before testing, the partial thromboplastin time of normal plasma was increased. Clq reduced the activation of HF by ellagic acid, as measured by the release ofp-nitroaniline from the synthetic substrate H-D-prolyl-L-phenylalanyl-L-arginine-p-nitroanilide dihydrochloride, an effect inhibited by monoclonal anti-human Clq murine IgG and by digestion of C1q by collagenase. Thus, Clq inhibits activation of HF in vitro in clot-promoting and amidolytic assays and suggests a regulatory mechanism for the inhibition of coagulation.

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Activation of Rabbit Hageman Factor by Homogenates of Cultured Rabbit Endothelial Cells

Abstract: A B S T R A C T Rabbit

Cited by 75 publications

References 34 publications

Experimental acute thrombotic stroke in baboons.

Experimental acute thrombotic stroke in baboons.

Studies on the Pathogenesis of the Adult Respiratory Distress Syndrome

Inhibition of the activation of Hageman factor (factor XII) by complement subcomponent C1q.

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