Platelet Factor 4: An Inhibitor of Collagenase

Hiti-Harper, Judith; Wohl, Herbert; Harper, Elvin

doi:10.1126/science.203038

Cited by 98 publications

(24 citation statements)

References 17 publications

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“…Especially, PDGF and platelet factor 4 (PF4) which are located in a-granules of megakaryocytes, are hypothesized to be responsible for the pathogenesis of idiopathic myelofibrosis (Bernabei et al, 1986;Castro-Malaspina, 1984;McCarthy, 1985). PDGF is an effective mitogen for fibroblasts (Heldin, 1992;Ross et al, 1986) whereas PF4 inhibits collagenase activity (Hiti-Harper, 1978).…”

Section: Discussionmentioning

confidence: 99%

The role of transforming growth factor‐β in PEG‐rHuMGDF‐induced reversible myelofibrosis in rats

et al. 1997

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Summary. Pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) injected at a suprapharmacologic dose (100 mg/kg) daily for 5 d in normal rats caused marked increases in marrow megakaryocytes and platelet counts at 6-8 d followed by gradual decreases to control levels at 10-20 d. Interestingly, in addition to the expected thrombopoiesis, PEG-rHuMGDF was associated with myelofibrosis with a predominance of reticulin fibres at day 10 followed by complete normalization by day 20. At 6-8 d, the levels of transforming growth factor-b1 (TGF-b1) in the extracellular fluid of the marrow, the platelet poor plasma, and the platelet extract were increased 23-, 7-and 2-fold, respectively. The elevated levels of TGF-b1 were gradually reduced to baseline levels at 13-20 d in accordance with the normalization of myelofibrosis and thrombopoiesis. An ultrastructural analysis showed that large fragments of megakaryocytes were deposited in the marrow parenchyma of PEG-rHuMGDF-treated rats at day 6. PEG-rHuMGDF administration at pharmacologic doses (1 and 10 mg/kg) did not induce the deposition of reticulin fibres in the marrow. These findings suggest that TGF-b1 leaked from megakaryocytes is involved in the development of the PEG-rHuMGDF-induced myelofibrosis and that this is a reversible process related to the regulation of the excess production of platelets.

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Section: Discussionmentioning

confidence: 99%

The role of transforming growth factor‐β in PEG‐rHuMGDF‐induced reversible myelofibrosis in rats

et al. 1997

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“…This platelet peptide has been shown to interfere with binding ofheparinlike molecules to antithrombin, thereby inhibiting the acceleration of enzymeinhibitor complex formation (8). PF4 also binds to various molecular components, including anticoagulantly inactive heparin (28), chondroitin 4-sulfate (29,30), chondroitin 6-sulfate (29), dermatan sulfate (29), low density lipoprotein receptor (31), collagenase (32), and serotonin (33). Thus, the above data cannot be used to identify heparinlike molecules on the endothelium that can accelerate antithrombin function.…”

Section: Discussionmentioning

confidence: 99%

Acceleration of thrombin-antithrombin complex formation in rat hindquarters via heparinlike molecules bound to the endothelium.

Marcum¹,

McKenney²,

Rosenberg³

1984

J. Clin. Invest.

332

127

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A s bstract. We have examined the role of heparinlike molecules in the regulation of coagulation by perfusing rat hindquarters with purified human thrombin and with its plasma inhibitor, antithrombin. Our data indicate that contact of the hemostatic components with the endothelium enhances the rate of thrombin-antithrombin complex formation by as much as 19-fold over the uncatalyzed rate of enzyme-inhibitor interaction. Heparinlike molecules are responsible for the antithrombin accelerating activity. The amount of thrombin-antithrombin complex generated within the hindlimb preparation after pretreatment of the vasculature with purified Flavobacterium heparinase or with addition of platelet Factor IV to the hemostatic components, was equal to the uncatalyzed levels. These heparinlike molecules appear to be tightly bound to the luminal surface of the endothelium, since they could not be detected within the physiologic buffer that was perfused through the animal. The above mucopolysaccharides function in a manner similar to commercial heparin, since modification of antithrombin at a site critical for heparin-dependent acceleration of the protease inhibitor resulted in a level of interaction product identical to the uncatalyzed amount. Finally, addition of diisofluorophosphate-thrombin to the enzyme perfusion stream reduced the amount of thrombin-antithrombin complex formed in the animal by 30-40%, which suggested that thrombin bound to the en-

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“…Some previously defined functions of PF4, including modulation of the activity of collagenase and elastase (13,14) and stimulation of PMN leukocyte and monocyte chemotaxis (15), appear to result from one or more complex molecular and cellular events. Other functions of PF4, such as the binding and neutralization of heparin (16), are determined largely by charge interactions.…”

Section: Discussionmentioning

confidence: 99%

Stimulation of histamine release from human basophils by human platelet factor 4.

Brindley¹,

Sweet²,

Goetzl³

1983

J. Clin. Invest.

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Platelet Factor 4: An Inhibitor of Collagenase

Cited by 98 publications

References 17 publications

The role of transforming growth factor‐β in PEG‐rHuMGDF‐induced reversible myelofibrosis in rats

The role of transforming growth factor‐β in PEG‐rHuMGDF‐induced reversible myelofibrosis in rats

Acceleration of thrombin-antithrombin complex formation in rat hindquarters via heparinlike molecules bound to the endothelium.

Stimulation of histamine release from human basophils by human platelet factor 4.

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