Active release of human platelet factor VIII-related antigen by adenosine diphosphate, collagen, and thrombin.

Koutts, Jerry; Walsh, PN; Plow, Edward F.; Fenton, John W.; Bouma, Bonno N.; Zimmerman, Theodore S.

doi:10.1172/jci109246

Cited by 165 publications

(58 citation statements)

References 27 publications

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“…2 a). The granular pattern of staining was similar to that found in platelet alpha granules (Fig. 2, e and f), which are known to contain vW protein (14,15).…”

Section: Resultssupporting

confidence: 76%

Biosynthesis of von Willebrand protein by human megakaryocytes.

Sporn¹,

Chavin²,

Marder³

et al. 1985

J. Clin. Invest.

248

130

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“…2 a). The granular pattern of staining was similar to that found in platelet alpha granules (Fig. 2, e and f), which are known to contain vW protein (14,15).…”

Section: Resultssupporting

confidence: 76%

Biosynthesis of von Willebrand protein by human megakaryocytes.

Sporn¹,

Chavin²,

Marder³

et al. 1985

J. Clin. Invest.

248

130

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“…In addition, TGF␤ platelets contain in their alphagranules numerous proteins, including adhesion factors, plasma proteins, coagulation factors, protease inhibitors (Davey and Luscher, 1968;Levine and Wohl, 1976;Nachman and Harpel, 1976;Koutts et al, 1978;Zucker et al, 1979;Plow and Collen, 1981), and the growth factors PDGF (Antoniades et al, 1979;Heldin et al, 1981), EGF/TGF␣ (Oka and Orth, 1983), and IGF . All three isoforms of PDGF, the AB heterodimer and the AA and BB homodimers, have been isolated from human platelets.…”

Section: Platelet-derived Growth Factors Stimulate Pancreatic Stellatmentioning

confidence: 99%

Platelet-Derived Growth Factors Stimulate Proliferation and Extracellular Matrix Synthesis of Pancreatic Stellate Cells: Implications in Pathogenesis of Pancreas Fibrosis

Luttenberger

Schmid‐Kotsas

Menke

et al. 2000

Laboratory Investigation

180

110

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SUMMARY:At present, the cell-cell interactions and molecular mechanisms of pancreas fibrogenesis are largely unknown. The purpose of this study was to investigate paracrine stimulatory loops between platelets and pancreatic stellate cells (PSC). Human PSC were obtained by outgrowth from fibrotic human pancreas. Native platelet lysate (nPL) and transiently acidified platelet lysate (aPL) were added to cultured PSC (passage 4 to 7) in the absence of serum. The synthesis of collagen types I and III and c-fibronectin (cFN) was demonstrated on protein (immunofluorescence and quantitative immunoassay) and mRNA (Northern blot) level. Using sections of human pancreas with acute pancreatitis, platelet aggregates in capillaries were demonstrated by transmission electron microscopy. nPL, and to an even greater extent aPL, significantly increased the synthesis of collagen types I and III and of c-FN (120 l/ml aPL increased collagen type I concentration in PSC supernatants by 1.99 Ϯ 0.17 times and c-FN of 2.49 Ϯ 0.28 times, mean Ϯ SD, n ϭ 3). nPL and aPL also significantly stimulated cell proliferation (increased bromodeoxyuridine (BrdU) incorporation by 6.4 Ϯ 0.78 times and 10 Ϯ 0.29 times, respectively). By preincubating aPL with transforming growth factor ␤ (TGF␤)-and platelet-derived growth factor (PDGF)-neutralizing antibodies and the TGF␤-latency associated peptide, respectively, TGF␤1 was identified as the main mediator stimulating matrix synthesis and PDGF as the responsible mitogen. Our data demonstrate that platelets contain fibrogenic mediators that stimulate proliferation (PDGF) and matrix synthesis (TGF␤1) of cultured PSC. We suggest that platelets and PSC cooperate in the development of pancreas fibrosis. (Lab Invest 2000, 80:47-55).

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“…While this study was in progress [25], Tracy et al [26] reported immunologic similarity of bovine platelet factor V to plasma factor V by immunodiffkion and radioimmunoassay, but no data were presented as to the molecular weight or electrophoretic migration. The similarity of platelet fibrinogen [27], factor VIII/vWf [28], the a subunits of factor XI11 [29], and fibronectin [30] to the corresponding plasma proteins has been demonstrated. Platelet factor V solubilized by a nonionic detergent in the presence of proteolytic and metabolic inhibitors exhibits and anodal mobility on immunoelectrophoresis.…”

Section: Discussionmentioning

confidence: 99%

Immunochemical Studies of Factor V of Bovine Platelets

1981

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lmmunochemical techniques were employed to investigate the molecular properties of bovine platelet factor V. An antiserum prepared against purified factor V rapidly inactivated platelet factor V, indicating that platelet factor V is antigenically related to plasma factor V. A reaction ofidentity between factor V in plasma and purified factor V was documented by immunodiffusion against an antibody to platelet factor V. When platelet factor V was extracted with Triton X-100 in the presence of protease inhibitors and subjected to immunoelectrophoresis against the antiserum to plasma factor V, a single antigenic component migrating toward the anode was observed. In the absence of protease inhibitors, following release by collagen or solubilization, platelet factor V appeared close to the origin suggesting proteolytic alteration. Platelet factor V released by collagen or extracted with Triton X-100 was activated by thrombin 7.4-fold and 4.5-fold respectively, compared to a 17-fold activation of factor V in plasma under identical conditions. The ability of thrombin to activate platelet factor V as well as the close correspondence of factor V activity and antigen released by collagen indicates that the molecule is largely in the unactivated form after release. A single component of molecular weight 270000 was seen when platelet factor V released by collagen was immunoprecipitated and subjected to dodecylsulphate gel electrophoresis. Factor V coagulant assays and immunoelectrophoresis of subcellular fractions showed that platelet factor V is localized primarily in the a-granules.Platelet factor V appears to be similar to, if not identical with, plasma factor V by the criteria of immunologic identity, similar electrophoretic mobility and virtually identical molecular weights.Bovine platelets contain factor V, an accelerator of the conversion of prothrombin [I]. Human platelets freed o f plasma by high speed centrifugation also possess factor-V activity [2-41. The factor-V activity of platelets was initially assumed to be due to adsorption of plasma factor V to the platelet surface [2]. However, Breederveld et al. [5] and Osterud et al. [6] demonstrated that gel-filtered platelets possess only minimal factor-\/ activity, and that freezing and thawing increase the activity significantly. Studies of Miletich et al. [7] demonstrated that factor X a binds to the platelet surface at sites which are identical to or require the presence of factor V. Their studies suggest that specific receptors for factor X a appear on the platelet surface only after the release reaction occurs [8]. Work from our laboratory has shown that human platelet factor V is localized in the a-granules and that optimal release requires the presence of ADP and the synthesis of prostaglandin intermediates 19, 101. All of the above studies were limited in that platelet factor V was measured functionally, and increased activity could be due to either an actual increase in factor V protein of the formation of a more active m ol ecule.Bovine plasma factor V...

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Active release of human platelet factor VIII-related antigen by adenosine diphosphate, collagen, and thrombin.

Cited by 165 publications

References 27 publications

Biosynthesis of von Willebrand protein by human megakaryocytes.

Biosynthesis of von Willebrand protein by human megakaryocytes.

Platelet-Derived Growth Factors Stimulate Proliferation and Extracellular Matrix Synthesis of Pancreatic Stellate Cells: Implications in Pathogenesis of Pancreas Fibrosis

Immunochemical Studies of Factor V of Bovine Platelets

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