The Nature and Action of the Thromboplastic (Zymoplastic) Substance of the Tissues

Howell, W. H.

doi:10.1152/ajplegacy.1912.31.1.1

Cited by 100 publications

(20 citation statements)

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“…The papers were removed after the front had ascended about 40 cm., which took two to three hours. Before staining, the pa- 3 Part No. C-4249-2X, Scientific Glass Co., Bloomfield, N. J.…”

Section: Methodsmentioning

confidence: 99%

Platelet Phosphatides: Their Separation, Identification, and Clotting Activity1

Marcus¹,

Spaet²

1958

J. Clin. Invest.

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“…The papers were removed after the front had ascended about 40 cm., which took two to three hours. Before staining, the pa- 3 Part No. C-4249-2X, Scientific Glass Co., Bloomfield, N. J.…”

Section: Methodsmentioning

confidence: 99%

Platelet Phosphatides: Their Separation, Identification, and Clotting Activity1

Marcus¹,

Spaet²

1958

J. Clin. Invest.

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“…It is now known that this is due to a specific interaction between the tissue extracts (tissue factor) and a plasma protein, factor VII (1, 2). Although the structure of tissue factor is not known, it has been clear for many years that it contains both a protein and lipid moiety (3). In a previous study on the lipid component of tissue factor, it was demonstrated that certain phospholipids were necessary for full biological activity to be achieved (4).…”

Section: Introductionmentioning

confidence: 99%

Characteristics and lipid requirements of coagulant proteins extracted from lung and brain: the specificity of the protein component of tissue factor

Nemerson¹

1969

J. Clin. Invest.

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A B S T R A C T Soluble proteins were prepared from bovine lung and brain which, when combined with phospholipids, had the biological characteristics of tissue factor. The proteins were solubilized from delipidated (heptane:butanol-extracted) acetone powders with deoxycholate, and precipitated by (NH4)2SO4 (30-60% saturation). These soluble proteins, which contained less than 1% phospholipid, were essentially inert in an assay for tissue factor. When they were recombined with phospholipids, however, activity increased by a factor of 500-1000. Phosphatidylethanolamine was the most active specific phospholipid, followed by phosphatidylcholine. Phosphatidylserine was inert. Mixed phospholipids were from two to four times more active than phosphatidylethanolamine. Maximum activity was obtained at phospholipid to protein ratios of 1.5: 1 (wt/wt), and when relipidation was performed in deoxycholate followed by dialysis against 0.05 M imidazole-0.375 M NaCl, pH 7.2.The proteins were characterized by gel filtration on Sephadex G-200; the activity eluted as a single peak with an apparent mol wt of 425,000. INTRODUCTIONWhen aqueous extracts derived from various tissues are added to plasma, the rate of coagulation after recalcification is markedly enhanced. It is now known that this is due to a specific interaction between the tissue extracts (tissue factor) and a plasma protein, factor VII (1, 2). Although the structure of tissue factor is not known, it has been clear for many years that it contains both a protein and lipid moiety (3). In a previous study on the lipid component of tissue factor, it was demonstrated that certain phospholipids were necessary for full biological activity to be achieved (4).Only some tissues contain significant amounts of tissue factor which strongly suggests that there are specific proteins within the active tissues that account for their coagulant activity. On the other hand, it has been stated that tissue factor is all, or almost all, lipid, (5, 6). Previously, we demonstrated that a lipid-poor protein obtained from brain tissue activated the extrinsic coagulant mechanism, i.e., it functioned as tissue factor (7).This reaction, however, occurred at a very slow rate, and it was therefore uncertain whether this protein represented a specific tissue factor protein, or a nonspecific protease.In The optimal conditions for the restitution of activity by phospholipids were determined for brain and lung proteins and were found to be essentially identical, as were their requirements for specific phospholipids. Preliminary characterization of the proteins was accomplished by gel filtration and ion exchange chromatography. The proteins had similar molecular weights (as determined by gel filtration), but behaved slightly differently on ion exchange chromatography. The chromatographic data suggest that within each organ there is but one active protein (or a family of closely related proteins), and that there may be molecular differences between the tissue factor proteins of lung and brain. METHODSPuri...

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“…The crude cephalin of Howell accelerated clotting (2), whereas the extraction of lipid from plasma by Macfarlane, Trevan and Attwood inhibited its coagulation (3). Many studies have stressed the role of phospholipids in coagulation.…”

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confidence: 99%