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S Niewiarowski

Publications and source records attributed to S Niewiarowski.

At least 127 records · Page 7Linked to original sources
PubMed1985

The interaction of human platelet thrombospondin with fibrinogen. Thrombospondin purification and specificity of interaction.

Human platelet thrombospondin (TSP) was purified to homogeneity by chromatography on fibrinogen coupled to cyanogen bromide-activated Sepharose. The yield of TSP was 1.3 mg or approximately 22% of that present in platelet-rich plasma as determined by radioimmunoassay. It analyzed on discontinuous sodium dodecyl sulfate gels as a single band having apparent molecular weights of 180,000 and greater than 400,000 under reducing and nonreducing conditions, respectively. Amino acid analysis gave results similar to previously published values. Antibodies raised in rabbits were monospecific as evaluated by radioimmunoassay. In double immunodiffusion tests, these antibodies gave one line of identity against TSP purified by this procedure and TSP purified by published procedures, confirming the identity of the material isolated. The protein possesses no lectin-like activity. The specificity of the TSP-fibrinogen interaction was investigated. TSP binding to fibrinogen-Sepharose occurred in the presence of EDTA, indicating that calcium and magnesium ions are not required for interaction of TSP with fibrinogen. The binding of TSP to fibrinogen-Sepharose was quantitatively blocked by pretreatment with an antibody to the cyanogen bromide cleavage fragment composed of residues 241-476 of the carboxyl-terminal end of the alpha chain of fibrinogen. Antibodies against the D and E domains of fibrinogen had no effect on the binding. Excess fibrinogen (30 mg/ml) added to platelet extract quantitatively inhibited binding of TSP to fibrinogen-Sepharose. TSP preferentially bound to uncross-linked fibrin, suggesting that the TSP-fibrinogen binding site is unavailable in cross-linked fibrin. These results indicate that TSP binds specifically to immobilized fibrinogen or uncross-linked fibrin through determinants present in the carboxyl-terminal portion of the alpha chain and that these interactions do not require calcium or magnesium ions.

Amino Acids↗
PubMed1985

Identification of PlAl alloantigen domain on a 66 kDa protein derived from glycoprotein IIIa of human platelets.

Incubation of platelets with chymotryptin leads to the exposure of fibrinogen receptors and to the appearance of a 66 kDa membrane component on the surface of platelets. Both glycoprotein IIIa (GP IIIa) and a 66 kDa component were precipitated from detergent extracts of solubilized, surface radiolabeled chymotrypsin-treated platelets by human anti-PlAl antisera. Moreover, the presence of the P1A1 antigen was identified on GP IIIa (but not on GP IIb) and on a 66 kDa protein by means of immunoblot procedures using platelet Triton X-114 extracts and these purified proteins. Anti-PlAl antiserum did not recognize GP IIIa on the surface of intact (untreated) platelets nor the 66 kDa protein on the surface of chymotrypsin-treated platelets of PlAl-negative individuals. The present data demonstrate directly that the 66 kDa protein is derived from GP IIIa and contains the PlAl alloantigen.

Antigens, Human Platelet↗
PubMed1985

Membrane fluidity and platelet fibrinogen receptor exposure by proteolytic enzymes.

Incubation of platelets with pronase or chymotrypsin results in the exposure of fibrinogen receptors. We determined that these enzymes did not affect the membrane fluidity as evaluated by the depolarization of the fluorescence of 1,6-diphenyl-1,3,5 hexatriene (DPH). There was no significant difference in either the depolarization or in its temperature dependence for control, pronase or chymotrypsin-treated platelets. Thus, it can be concluded that the exposure of fibrinogen receptors on the platelet surface by proteolytic enzymes does not depend on the changes of membrane fluidity. We also propose that the proteolytic enzymes do not cause a major alteration in the extent of protein chains embedded in the lipid layers of the platelet membranes.

Blood Platelets↗
PubMed1985

Nomenclature of secreted platelet proteins--report of the Working Party on Secreted Platelet Proteins of the Subcommittee on Platelets.

Standard nomenclature for a number of secreted platelet proteins was agreed upon by The Working Party on Secreted Platelet Proteins of the Subcommittee on Platelets. Platelet factor 4 will continue to be used for the molecule with high heparin affinity, subunit molecular weight of 7780, and the described amino acid sequence. beta-Thromboglobulin will be used to designate beta-Thromboglobulin (81 amino acids/subunit, beta-mobility on cellulose-acetate electrophoresis, pI 7), low-affinity platelet factor 4 (85 amino acids/subunit, gamma-mobility on cellulose-acetate electrophoresis, pI 8), and platelet basic protein (94 amino acids/subunit, pI 10) when these are measured immunologically in plasma, but that thromboglobulin with a superscript designation of the pI should be used when assays are conducted on samples after isoelectric focusing, and a subscript amino-terminal amino acid can be added when a purified protein is described. Thrombospondin will continue to be the designation for the high molecular weight trimer that has previously been called thrombospondin or glycoprotein G. Platelet derived growth factor will be used for the group of closely related proteins of molecular weight about 30,000 and isoelectric point about 10.

Animals↗
PubMed1985

Interaction of platelet factor 4 with human platelets.

Human washed resting platelets bound 125I-labeled platelet factor 4 in a reaction which was saturable and approached equilibrium within 15-30 min. Scatchard plot analysis of the binding isotherms suggested a single class of specific binding sites. Excess of unlabeled protein and low- and high-affinity heparin competed for platelet factor 4 binding sites on the platelet surface and caused a partial displacement of this molecule. Anti-platelet factor 4 Fab fragments caused inhibition of binding of 125I-platelet factor 4 to platelets. Most of the labeled platelet factor 4 which was bound to intact platelets was recovered in the Triton X-100-insoluble cytoskeletal fraction prepared from the same platelets after their stimulation by thrombin. The association with the cytoskeleton was inhibited by anti-platelet factor 4 Fab fragments and by low-affinity heparin. Anti-platelet factor 4 125I-labeled Fab fragments bound to resting platelets, and this binding was greatly increased following platelet stimulation with thrombin. This suggested that endogenously secreted platelet factor 4 also binds to the platelet surface. No significant binding to platelets of 125I-labeled beta-thromboglobulin and 125I-labeled anti-beta-thromboglobulin Fab fragments was observed. Fab fragments of monospecific anti-human platelet factor 4 antibody raised in rabbits inhibited platelet aggregation and secretion induced by low concentrations of thrombin. Fab fragments of anti-beta-thromboglobulin antibody had no inhibitory effect. We suggest that the binding of alpha-granule-derived platelet factor 4 to the specific sites on the surface of platelets may modulate platelet aggregation and secretion induced by low levels of platelet agonists.

Adenosine Diphosphate↗
PubMed1985

Radioimmunoassay of human platelet thrombospondin: different patterns of thrombospondin and beta-thromboglobulin antigen secretion and clearance from the circulation.

A method for radioimmunoassay of human thrombospondin was developed. Monospecific precipitating anti-human thrombospondin antibody was raised in rabbits after injection of thrombospondin purified by fibrinogen-agarose chromatography and preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The linear portion of the thrombospondin radioimmunoassay standard curve was 0.5 to 20 ng/ml. Normal platelets and platelet-poor plasma contained 28,900 +/- 14,500 ng thrombospondin per 10(9) platelets and 60.6 +/- 10.7 ng/ml (mean +/- SD), respectively. Using radioimmunoassays for beta-thromboglobulin and thrombospondin antigens, we compared platelet location and secretion of these proteins. Both antigens shared similar distributions in platelet subcellular fractions with the largest amount localized to platelet alpha-granules. With thrombin (0.25 U/ml) as a platelet agonist, 62.4% and 19.5% of total beta-thromboglobulin and thrombospondin, respectively, were secreted from suspensions of washed human platelets. Because only 20% of the total platelet thrombospondin was secreted, further studies were initiated to determine whether the remaining thrombospondin became localized on the activated platelets membrane. 125I-Fab antithrombospondin specifically bound to activated platelets but not to unstimulated platelets. In contrast, 125I-Fab anti-beta-thromboglobulin did not bind to activated platelets. Plasma clearance of human beta-thromboglobulin (half-life fast 7.6 minutes, slow 56.6 minutes) and of human thrombospondin (half-life fast 29.9 minutes, slow 190 minutes) followed a biphasic exponential curve. In conclusion, both beta-thromboglobulin and thrombospondin are located in platelet alpha-granules, but they show a different pattern of secretion and expression on the platelet membrane and plasma clearance.

Animals↗
PubMed1985

Loss of fibrinogen receptors from the platelet surface during simulated extracorporeal circulation.

In vitro recirculation of fresh human heparinized blood in an extracorporeal circuit with a membrane oxygenator decreased fibrinogen-induced platelet aggregation and diminished the number of fibrinogen receptors and glycoprotein IIb/IIIa (GPIIb/GPIIIa) antigenic sites on the platelet surface. In seven experiments, the mean +/- SD Km value for fibrinogen (i.e., molar concentration of fibrinogen required to cause 50% of the maximal rate of aggregation) was 1.58 X 10(-7) mol/L +/- 0.68 X 10(-7) mol/L. After recirculation, this value increased to 3.8 X 10(-7) mol/L +/- 1.94 X 10(-7) mol/L (P less than or equal to 0.025). The maximal aggregation rate of chymotrypsin-treated platelets decreased by 40% after 2 hours of recirculation (P less than or equal to 0.025). The number of fibrinogen receptors on platelets, which were treated with chymotrypsin after a recirculation, decreased from 41,370 +/- 24,000 to 13,230 +/- 10,230/platelet under the same conditions (P less than or equal to 0.025). The number of antigenic sites for monoclonal antibody reacting with GPIIb/GPIIIa complex of adenosine diphosphate-stimulated platelets decreased from 34,200 +/- 5,940 to 19,500 +/- 9,680/platelet after recirculation (P less than or equal to 0.025). Prostaglandin E1 (0.3 mumol/L) in the perfusion circuit preserved the ability of platelets to react with fibrinogen. In conclusion, the loss of fibrinogen receptors from the surface of platelet membranes results from the interaction of platelets with the surfaces of perfusion circuits.

Adenosine Diphosphate↗
PubMed1985

Aggregation of chymotrypsin-treated thrombasthenic platelets is mediated by fibrinogen binding to glycoproteins IIb and IIIa.

Previous experiments demonstrated that chymotrypsin, but not adenosine diphosphate (ADP), exposed fibrinogen binding sites on platelets from patients with Glanzmann's thrombasthenia. Three of these patients have been reexamined, and previous observations were confirmed. The quantity of iodine 125-labeled glycoprotein IIb (GPIIb) and glycoprotein IIIa (GPIIIa) on the platelets of these patients was considerably less than normal but was detectable by immunoprecipitation, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and autoradiography. The amount of residual GPIIb and GPIIIa as measured by binding studies with radiolabeled monoclonal antibodies was between 3% and 12% of the normal value. Platelet suspensions from these patients did not aggregate with fibrinogen and did not bind 125I-fibrinogen on stimulation with ADP. However, incubation of these platelets with chymotrypsin or pronase resulted in fibrinogen binding and platelet aggregation. Monoclonal antibodies specific for the GPIIb-GPIIIa complex blocked both the fibrinogen binding and the aggregation of enzyme-treated platelets. The treatment of washed platelets of a fourth thrombasthenic patient with ADP or with chymotrypsin failed to result in fibrinogen binding and aggregation. However, the level of GPIIb and GPIIIa on these platelets as measured by a Western blot technique and by monoclonal antibody binding amounted to less than 0.35% to 0.5% of normal values. In conclusion, fibrinogen binding sites exposed on thrombasthenic platelets by chymotrypsin are derived from GPIIb-GPIIIa molecules. Aggregation of chymotrypsin-treated thrombasthenic platelets by fibrinogen appears to represent a sensitive test for detection of functionally active GPIIb-GPIIIa complex on the platelet surface.

Antibodies, Monoclonal↗
PubMed1985

Loss of platelet alpha 2-adrenergic receptors during simulated extracorporeal circulation: prevention with prostaglandin E1.

Cardiopulmonary bypass prolongs bleeding time and increases postoperative blood loss. During in vitro recirculation in an extracorporeal circuit containing a membrane oxygenator and primed with fresh heparinized human blood, we previously observed thrombocytopenia, impaired platelet aggregation, and depletion of granular contents, all of which were prevented with prostaglandin E1 (PGE1). To investigate these changes further, we studied the number and affinity of platelet alpha 2-adrenergic receptors by measuring the binding of 3H-yohimbine. Before recirculation, we found 235 +/- 28 alpha 2-adrenergic receptors per platelet, a Kd of 3.37 +/- 0.78 nmol/L, complete aggregation with 1.04 mumol/L epinephrine, and a platelet count of 281,000 +/- 33,000 microliters-1. After 2 minutes of recirculation, 9.44 mumol/L epinephrine was required to produce complete aggregation, and the platelet count was 104,000 +/- 22,000 microliters-1 (44% of control). The number of binding sites significantly decreased to 139 +/- 16 per platelet, but the affinity did not change (Kd = 3.78 +/- 0.44 nmol/L). After 2 hours of recirculation, the platelet count had increased to 123,000 +/- 21,000 microliters-1. However, epinephrine did not induce platelet aggregation even at 100 mumol/L. Moreover, alpha 2-adrenergic binding sites were not detectable, and affinity for yohimbine could not be calculated. Two minutes after PGE1 0.3 mumol/L was added to the circuit, platelet numbers, response to epinephrine, alpha 2-adrenergic binding sites per platelet, and affinity for yohimbine were not significantly different from control values. At 2 hours, the number of alpha 2-adrenergic sites was not significantly changed from control, but the affinity of yohimbine for platelets was significantly decreased 2.5-fold.(ABSTRACT TRUNCATED AT 250 WORDS)

Alprostadil↗
PubMed1984

Association of fibrin with the platelet cytoskeleton.

We have previously postulated that surface membrane proteins become specifically associated with the internal platelet cytoskeleton upon platelet activation (Tuszynski, G.P., Walsh, P.N., Piperno, J., and Koshy, A. (1982) J. Biol. Chem. 257, 4557-4563). Four lines of evidence are in support of this general hypothesis since we now show that platelet surface receptors for fibrin become specifically associated with the platelet Triton-insoluble cytoskeleton. 1) Fibrin was detected immunologically in the washed Triton-insoluble cytoskeletons of thrombin-activated platelets under conditions where fibrin polymerization and resultant precipitation was blocked with Gly-Pro-Arg-Pro, a synthetic peptide that inhibits polymerization of fibrin monomer. 2) Radiolabeled fibrin bound to thrombin-activated platelets and became associated with the cytoskeleton. 3) The amount of radiolabeled fibrin bound to thrombin-activated thrombasthenic platelets and their cytoskeletons amounted to about 20% of the fibrin bound to thrombin-activated control platelets and their cytoskeletons. 4) The association of fibrin with cytoskeletons and with the platelet surface was nearly quantitatively blocked by an antibody prepared against cytoskeletons (anti-C), an antibody against isolated membranes of Pronase-treated platelets (anti-M1), and a monoclonal antibody to the platelet surface glycoprotein complex, GPIIb-GPIII (anti-GPIII). These antibodies blocked ADP and thrombin-induced platelet aggregation as well as thrombin-induced clot retraction. Analysis of the immunoprecipitates obtained with anti-C, anti-M1, and anti-GPIII from detergent extracts of 125I-surface labeled platelets revealed that these antibodies recognized GPIIb-GPIII. These data suggest that thrombin activation of platelets results in the specific association of fibrin with the platelet cytoskeleton, that this association may be mediated by the GPIIb-GPIII complex, and that these mechanisms may play an important role in platelet aggregation and clot retraction induced by thrombin.

Blood Platelets↗
PubMed1984

Comparison of platelet fibrinogen receptors on intact and proteolytically-treated platelets by use of an anti-glycoprotein IIIa monoclonal antibody (MA 123).

A murine monoclonal antibody (MA 123) was selected by screening 153 supernatants of hybridoma cells secreting anti-human platelet antibodies for their ability to inhibit the fibrinogen-induced aggregation of chymotrypsin-treated platelets. MA 123 inhibited the binding of 125I-fibrinogen to ADP-stimulated intact human platelets and to platelets treated with chymotrypsin or pronase. Moreover, it inhibited the fibrinogen-induced aggregation of these platelet suspensions. The degree of inhibition was similar in each of the three types of platelets tested. The interactions of MA 123 with the 125I-labeled surface components of intact and chymotrypsin-treated platelets were studied by immunoprecipitation using Staphylococcus aureus coated with goat anti-mouse IgG, followed by SDS-polyacrylamide gel electrophoresis and autoradiography. MA 123 precipitated the glycoprotein IIb-glycoprotein IIIa (GPIIb-GPIIIa) complex from the surface of detergent solubilized intact human platelets; and it precipitated GPIIIa from the surface of chymotrypsin-treated platelets. Partially purified GPIIIa was also immunoprecipitated by MA 123. Our data suggest that the exposure of fibrinogen receptors by ADP, chymotrypsin or pronase, is associated with alterations of GPIIIa on the platelet surface.

Adenosine Diphosphate↗
PubMed1984

Partial purification and characterization of porcine platelet-derived growth factor (PDGF).

Platelet derived growth factor (PDGF) has been partially purified from porcine platelets. Purification steps included heparin-agarose chromatography of the material released by thrombin-stimulated washed porcine platelets and Blue-Sepharose chromatography. Preparative isoelectric focusing showed that isoelectric point of porcine PDGF is at pH 10.0-11.0 and elution experiments from sodium dodecyl sulfate (SDS) polyacrylamide gels indicated that its molecular weight is close to 30 kD. The immunoglobulin fraction prepared from anti-human PDGF serum inhibited the mitogenic activity of porcine PDGF. These experiments suggest a homology of porcine and human PDGF. Porcine platelet factor 4 and porcine platelet basic protein were devoid of significant mitogenic activity.

Animals↗
PubMed1984

Identification of human platelet membrane fibrinogen receptors by immunochemical techniques.

The fibrinogen receptors of platelets were investigated with the use of three types of anti-platelet membrane antibodies and three types of platelets. We found that antisera raised in rabbits against membranes prepared from human intact, chymotrypsin- or pronase-treated platelets inhibited the fibrinogen-induced aggregations of ADP-stimulated intact platelets, chymotrypsin-treated platelets and pronase-treated platelets. These antisera also blocked the binding of 125I-fibrinogen to ADP-stimulated intact, chymotrypsin-treated, and pronase-treated platelets. These results suggest that all three antisera blocked the interaction of fibrinogen with its receptor on the surface of the three types of platelets studied. Fibrin clot retraction by intact platelets was also inhibited by these three antibodies indicating an important role of platelet membrane proteins in clot retraction. As demonstrated by techniques using 125I-surface labeling, Staphylococcus aureus immunoprecipitation, SDS-polyacrylamide gel electrophoresis and autoradiography, anti-intact platelet membrane antibody immunoprecipitated the membrane glycoproteins GPIIb, GPIII and a protein with an apparent molecular weight of 66 000 from detergent solubilized surface 125I-iodinated chymotrypsin-treated platelets. Anti-chymotrypsin and anti-pronase-treated platelet membrane antisera immunoprecipitated mostly GPIII and the 66 000 molecular weight protein from detergent solubilized, surface 125I-iodinated chymotrypsin-treated platelets. The 66 000 Mr protein was not found on the surface of intact (unstimulated) platelets which do not bind 125I-fibrinogen and are not aggregated by fibrinogen without the prior addition of ADP. The ability of anti-platelet membrane antibodies to block fibrinogen-induced platelet aggregation and fibrinogen binding to platelets correlated with their ability to immunoprecipitate a 66 000 Mr protein from the platelet surface. It is proposed that the 66 000 Mr protein may be the fibrinogen binding domain of GPIII which becomes permanently exposed on the surface of chymotrypsin and pronase-treated platelets following proteolysis and which becomes exposed upon stimulation of intact platelets by agents such as ADP.

Autoradiography↗
PubMed1983

Inhibition of fibrinogen receptor-mediated platelet aggregation by heterologous anti-human platelet membrane antibody. Significance of an Mr = 66,000 protein derived from glycoprotein IIIa.

Heterologous anti-human platelet membrane antisera were raised in rabbits against membranes prepared from human intact or chymotrypsin- or pronase-treated platelets. Anti-intact, anti-chymotrypsin, and anti-pronase-treated platelet membrane antibodies (IgG and Fab fragments) inhibited the fibrinogen-induced aggregation of ADP-stimulated platelets and of chymotrypsin-treated platelets. The specific binding of 125I-fibrinogen to these platelets was also inhibited. As revealed by the sodium dodecyl sulfate-polyacrylamide gel electrophoresis of 125I-surface-radiolabeled platelet proteins and by the electrophoresis of the immunoprecipitates prepared from these labeled proteins, predominant components on the surface of intact platelets were glycoproteins IIb and IIIa. These proteins were immunoprecipitated by all three antibodies. In addition, chymotrypsin-treated platelets contained an Mr = 66,000 protein on their surface that was also immunoprecipitated by the three types of anti-platelet membrane antibodies. The appearance of this Mr = 66,000 protein on the surface of chymotrypsin-treated platelets correlated with the exposure of fibrinogen receptors on the platelet surface as evidenced by the increased platelet aggregation and the enhanced 125I-fibrinogen binding shown by chymotrypsin-treated platelets. The origin of the Mr = 66,000 protein labeled on chymotrypsin-treated platelets was studied by first labeling intact platelets with 125I and then treating these platelets with chymotrypsin. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the total labeled proteins present after chymotrypsin treatment and those immunoprecipitated by anti-pronase-treated platelet membrane antibody from detergent extracts of chymotrypsin-treated platelets suggested that the Mr = 66,000 protein was a proteolytic cleavage product of glycoprotein IIIa. Analysis on sodium dodecyl sulfate gels of the major chymotryptic cleavage products of partially purified glycoprotein IIIa and analysis of the peptide of glycoprotein IIIa immunoprecipitated by anti-pronase-treated platelet membrane antibody revealed that the Mr = 66,000 protein produced by chymotrypsin on the platelet surface was the major chymotryptic cleavage product of glycoprotein IIIa. We propose a hypothesis that the Mr = 66,000 is a part of glycoprotein IIIa present on the surface of proteolytically treated platelets and it may function in fibrinogen binding and fibrinogen-induced platelet aggregation and that the 66,000-dalton region of glycoprotein IIIa in intact platelets may represent the fibrinogen-binding domain of glycoprotein IIIa.

Adenosine Diphosphate↗
PubMed1983

Fibrinogen interaction with platelet receptors.

In summary: Incubation of platelets with ADP or proteolytic enzymes (chymotrypsin or pronase) results in an exposure of two classes of specific binding sites on platelet surface: low and high affinity fibrinogen receptors. Fibrinogen interaction with these receptors results in platelet aggregation. High affinity fibrinogen receptors are not exposed on thrombasthenic platelets stimulated by ADP but are rendered available on chymotrypsin-treated thrombasthenic platelets; low affinity receptors cannot be exposed by ADP or chymotrypsin on these platelets. Availability of high affinity fibrinogen receptors on thrombasthenic platelets may depend on the residual glycoprotein IIIa. Fibrinogen receptors appear to be associated with glycoproteins IIb, IIIa and a 66,000 Mr platelet membrane component that is exposed during proteolysis of platelet membranes. Some of the platelet-binding sites on the fibrinogen molecule appear to be associated with the COOH-terminal portion of the gamma chain (gamma 374-411). Additional binding sites may also be located in the COOH-terminal portion of the A alpha chain. The conformation of the fibrinogen molecule may be important in its interaction with platelets. Platelet aggregation may result from bridging platelets by fibrinogen molecule in the presence of bivalent cations. In conclusion, platelet interaction with fibrinogen is a complex process involving different binding sites of the fibrinogen molecule. Our own data and review of literature suggest that platelet-interaction with fibrinogen is of major significance in hemostasis.

Adenosine Diphosphate↗
PubMed1983

Human platelet secreted proteins and prostacyclin production by bovine aortic endothelial cells.

The effects of specific human platelet-secreted proteins on prostacyclin (PGI2) production by primary cultures of bovine aortic endothelial cells have been studied. Cells were incubated with various concentrations of highly purified preparations of platelet factor 4 (PF4), low-affinity platelet factor 4 (LA-PF4), beta-thromboglobulin (beta TG), platelet basic protein (PBP), and partially purified platelet-derived growth factor (PDGF) in the presence or absence of arachidonic acid (AA). The amount of 6-Keto-PGF1 alpha, the stable degradation product of PGI2, was determined in the cell incubation medium by means of a specific radioimmunoassay. Short-term (15 min) incubation of cell monolayers with either LA-PF4 or beta TG slightly reduced 6-keto-PGF1 alpha production. The effect was not dose-related and could not be observed after prolonged (24 hr) incubation of the cells with the same proteins. It was not seen in the cell suspensions. Moreover, 6-keto-PGF1 alpha production stimulated by AA was not affected by incubation with either of the proteins. PF4 and PBP had no significant effect on 6-keto-PGF1 alpha production by endothelial cells. Human PDGF showed a slight tendency to stimulate 6-keto-PGF1 alpha release when cells were incubated for 24 hr with the protein; however, PDGF did not potentiate the stimulatory effect of AA on 6-keto-PGF1 alpha release by the cells. We suggest that platelet-derived proteins exert only a moderate and possibly nonspecific effect on PGI2 production by endothelial cells.

6-Ketoprostaglandin F1 alpha↗