Binding of Aggregated Immunoglobulins to the Human Platelet Fc Receptors: A Mechanism of Platelet to Platelet Bridging

1987 ◽  
Vol 58 (04) ◽  
pp. 966-970 ◽  
Author(s):  
Anwar Parbtani ◽  
William F Clark ◽  
Anita Caveney ◽  
Bruce Reid
Keyword(s):  
Platelet Aggregation ◽  
Fc Receptors ◽  
Human Platelets ◽  
Minimum Concentration ◽  
Release Reaction ◽  
Aggregation Response ◽  
Aggregated Immunoglobulins ◽  
Platelet Aggregates ◽  
Induced Aggregation ◽  
Aggregation Of Platelets

SummaryAggregated immunoglobulins react with human platelets by occupying the Fc receptors present on their surface, inducing aggregation and the release reaction. We studied the effect of heat aggregated gammaglobulins (HAGG) on ADP-induced aggregation of platelets. We used the minimum concentration of ADP required to induce a reversible aggregation of platelets without any substantial amount of serotonin (14C 5HT) release. EDTA (5 mM) added at the peak of platelet aggregation resulted in rapid deaggrcgation ot these platelets. However, incubation of platelets with HAGG at a dose that did not by itself induce any aggregation or release reaction, followed by ADP addition resulted in an irreversible platelet aggregation of greater magnitude accompanied by a substantial release of 14C-5HT. The addition of EDTA at the peak of platelet aggregation failed to deaggregate these platelets. To determine whether the augmented aggregation response and the inhibition of deaggiega-tion was due to HAGG or a consequence of platelet release products, we used thrombin-degranulated platelets. The augmented aggregation response and the inhibition of deaggregation due to HAGG and ADP could be demonstrated using these platelets. To confirm that the binding of HAGG to the platelet Pc receptors was responsible for these observations, we incubated platelets with an excess of Fc fragments of IgG prior to the addition of HAGG and ADP. This abolished the aggregation response observed previously. From this study we conclude that interplatelet bridging by HAGG renders the platelets hyperag-gregable and appears to be a mechanism involved in maintaining platelet aggregates.

Ticlopidine Facilitates the Deaggregation of Human Platelets Aggregated by Thrombin

1994 ◽  
Vol 71 (01) ◽  
pp. 091-094 ◽  
Author(s):  
M Cattaneo ◽  
B Akkawat ◽  
R L Kinlough-Rathbone ◽  
M A Packham ◽  
C Cimminiello ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Platelet Aggregation ◽  
Prostaglandin E1 ◽  
Human Platelet ◽  
Adenosine Diphosphate ◽  
Human Platelets ◽  
Before And After ◽  
Normal Human ◽  
Platelet Aggregates ◽  
Induced Aggregation

SummaryNormal human platelets aggregated by thrombin undergo the release reaction and are not readily deaggregated by the combination of inhibitors hirudin, prostaglandin E1 (PGE1) and chymotrypsin. Released adenosine diphosphate (ADP) plays an important role in the stabilization of thrombin-induced human platelet aggregates. Since ticlopidine inhibits the platelet responses to ADP, we studied thrombin-induced aggregation and deaggregation of 14C-serotonin-labeled platelets from 12 patients with cardiovascular disease before and 7 days after the oral administration of ticlopidine, 250 mg b.i.d. Before and after ticlopidine, platelets stimulated with 1 U/ml thrombin aggregated, released about 80–90% 14C-serotinin and did not deaggregate spontaneously within 5 min from stimulation. Before ticlopidine, hirudin (5× the activity of thrombin) and PGE1 (10 μmol/1) plus chymotrypsin (10 U/ml) or plasmin (0.06 U/ml), added at the peak of platelet aggregation, caused slight or no platelet deaggregation. After ticlopidine, the extent of platelet deaggregation caused by the same inhibitors was significantly greater than before ticlopidine. The addition of ADP (10 μmol/1) to platelet suspensions 5 s after thrombin did not prevent the deaggregation of ticlopidine-treated platelets. Thus, ticlopidine facilitates the deaggregation of thrombin-induced human platelet aggregates, most probably because it inhibits the effects of ADP on platelets.

Effects of Bupranolol, a New β-Blocker, on Platelet Functions of Rabbit and Human in Vitro

1976 ◽  
Vol 36 (02) ◽  
pp. 376-387 ◽  
Author(s):  
Teruhiko Umetsu ◽  
Kazuko Sanai ◽  
Tadakatsu Kato
Keyword(s):  
Platelet Aggregation ◽  
Platelet Adhesion ◽  
Human Platelets ◽  
Rabbit Platelet ◽  
Rabbit Platelets ◽  
Β Blocker ◽  
Platelet Aggregates ◽  
Induced Aggregation ◽  
Platelet Functions

SummaryThe effects of bupranolol, a new β-blocker, on platelet functions were investigated in vitro in rabbits and humans as compared with propranolol, a well-known β-blocker. At first, the effect of adrenaline on ADP-induced rabbit platelet aggregation was studied because adrenaline alone induces little or no aggregation of rabbit platelets. Enhancement of ADP-induced rabbit platelet aggregation by adrenaline was confirmed, as previously reported by Sinakos and Caen (1967). In addition the degree of the enhancement was proved to be markedly affected by the concentration of ADP and to increase with decreasing concentration of ADP, although the maximum aggregation (percent) was decreased.Bupranolol and propranolol inhibited the (adrenaline-ADP-)induced aggregation of rabbit platelets, bupranolol being approximately 2.4–3.2 times as effective as propranolol. Bupranolol stimulated the disaggregation of platelet aggregates induced by a combination of adrenaline and ADP, but propranolol did not. Platelet adhesion in rabbit was also inhibited by the β-blockers and bupranolol was more active than propranolol. With human platelets, aggregation induced by adrenaline was inhibited by bupranolol about 2.8–3.3 times as effectively as propranolol.From these findings. We would suggest that bupranolol might be useful for prevention or treatment of thrombosis.

Requirement Of Fibrinogen And Calcium For Inter-Platelet Bridges In Platelet Aggregation: A Hypothesis

1981 ◽  
Author(s):  
Elizabeth Kornecki ◽  
Stefan Niewiarowski
Keyword(s):  
Platelet Aggregation ◽  
Binding Sites ◽  
Proteolytic Enzymes ◽  
Divalent Cations ◽  
Platelet Surface ◽  
Fibrinogen Binding ◽  
Platelet Aggregates ◽  
High Concentrations ◽  
Induced Aggregation ◽  
Aggregation Of Platelets

Fibrinogen and calcium are required for the aggregation of platelets stimulated by ADP or pre-treated with proteolytic enzymes. Specific platelet surface fibrinogen binding sites (receptors) are exposed after platelets are stimulated by ADP or pre-treated with Chymotrypsin or pronase. It has previously been shown in our laboratory that an intact, symmetrical fibrinogen molecule is essential for fibrinogen binding and fibrinogen-induced aggregation of both ADP-stimulated and proteolytically-treated platelets. Here we propose that the mechanism by which fibrinogen and calcium aggregate platelets is by forming inter-platelet bridges linking the fibrinogen receptors of adjacent platelets together. In support of this proposition are the following new lines of evidence: 1) The fibrinogen-induced aggregations of ADP-stfiliulated or proteolytically-treated platelets are inhibited by high concentrations of fibrinogen (Ki=2.6 and 8.5 × 10 5M, respectively). The fibrinogen binding sites on adjacent platelets, at these concentrations, would be saturated by fibrinogen and therefore no inter-platelet fibrinogen bridges could be formed to hold the platelets together. 2) ADP-stimulated or chymotrypsin-treated platelets aggregated by fibrinogen are deaggregated by Chymotrypsin or pronase and this deaggregation coincides with the loss of 125I-fibrinogen from the platelet surface. 3) Preincubation of platelets with EDTA results in inhibition of both platelet aggregation and 125I-fibrinogen binding. Following the aggregations of ADP-stimulated or of chymotrypsin-treated platelets by fibrinogen, the addition of EDTA to the platelet aggregates results in both their deaggregation and their loss of bound 125I-fibrinogen. Thus it appears that divalent cations, especially calcium, are essential for the formation of fibrinogen-linked platelet aggregates.

Inhibition of ADP-Induced Platelet Aggregation by Adenosine Tetraphosphate

1976 ◽  
Vol 36 (02) ◽  
pp. 388-391 ◽  
Author(s):  
Margaret J. Harrison ◽  
R Brossmer
Keyword(s):  
Platelet Aggregation ◽  
Inhibitory Action ◽  
Platelet Rich Plasma ◽  
Release Reaction ◽  
Induced Aggregation ◽  
Aggregation Of Platelets

SummaryIn contrast to previous reports, highly purified adenosine tetraphosphate (AP4) does not induce the aggregation of platelets but inhibits the aggregation and release reaction in platelet-rich plasma promoted by ADP. The inhibitory action of AP4 on the aggregation by ADP is compared with that of AMP and ATP. The data presented suggest a competitive manner of inhibition of the ADP-induced aggregation by AP4.

Thrombin Interaction with Human Platelets Potentiation of Thrombin-induced Aggregation and Release by Inactivated Thrombin

1974 ◽  
Vol 32 (01) ◽  
pp. 207-215 ◽  
Author(s):  
David R. Phillips
Keyword(s):  
Platelet Aggregation ◽  
Binding Sites ◽  
Human Platelet ◽  
Adenosine Diphosphate ◽  
Human Platelets ◽  
Induce Platelet Aggregation ◽  
Release Reaction ◽  
Proteolytic Site ◽  
Induced Aggregation ◽  
Inhibited Enzyme

SummaryThe possibility that thrombin acts on platelets by a mechanism other than proteolysis was investigated. The proteolytic site of thrombin was modified with phenylmethylsulfonyl fluoride (PMSF). This modified enzyme did not induce platelet aggregation or the platelet release reaction. Platelets were then incubated with the inactivated enzyme (PMS-thrombin) and later with active thrombin. In this sequence of incubation, PMS-thrombin enhanced not only platelet aggregation induced by active thrombin but also the thrombin-induced release reaction. Preincubation with PMS-thrombin was essential for this enhancement as the inhibited enzyme did not affect aggregation if added after active thrombin. The effect of PMS-thrombin was limited to thrombin-induced reactions of the platelet. The inhibited enzyme had no effect on aggregation induced by adenosine diphosphate or collagen, or on thrombininduced coagulation of fibrinogen. These results suggest (1) that both proteolytic and binding sites for thrombin are present on the human platelet plasma membrane ; and (2) that interaction of thrombin with the binding site potentiates the activity of the proteolytic site.

scholarly journals Human platelet activation by C3a and C3a des-arg.

1983 ◽  
Vol 158 (2) ◽  
pp. 603-615 ◽  
Author(s):  
M J Polley ◽  
R L Nachman
Keyword(s):  
Platelet Aggregation ◽  
Analysis Of Variance ◽  
Platelet Activation ◽  
Human Platelet ◽  
Human Platelets ◽  
Serotonin Release ◽  
Release Reaction ◽  
C Terminus ◽  
Induced Aggregation ◽  
Synergistic Reaction

C3a liberated from C3 by treatment with C3 convertase (or by trypsin) induced aggregation of gel-filtered human platelets and stimulated serotonin release. At concentrations of 10(-10) M to 8 X 10(-12) M, C3a induced aggregation when added alone to platelets. However, at lower concentrations (2 X 10(-12) M) C3a did not aggregate platelets directly but exhibited highly significant synergism (two-way analysis of variance P less than 0.0001) with ADP in mediating platelet aggregation and release of serotonin. Removal of the C-terminus arginine from C3a abolished anaphylotoxin activity but did not affect the platelet-stimulating activity of the peptide. C3a and C3a des-arg were equally reactive in mediating platelet aggregation and release of serotonin. Further C3a and C3a des-arg exhibited synergism with ADP of equal significance in both aggregation and the release reaction. The concentrations of C3a required for the platelet-stimulating activity involve relatively small number of molecules per platelet (4,000-10,000 for the synergistic reaction with ADP). These data suggest the possibility of a C3a (C3a des-arg) receptor on human platelets. This premise is strengthened by the demonstration ultrastructurally of C3a on the platelet membrane subsequent to C3a stimulation.

Platelet Monoamine Oxidase and Epinephrine-Induced Platelet Aggregation

1978 ◽  
Vol 40 (01) ◽  
pp. 037-042 ◽  
Author(s):  
Ennio C Rossi ◽  
Gerlinde Louis ◽  
Martha Bieber ◽  
E Albert Zeller
Keyword(s):  
Platelet Aggregation ◽  
Monoamine Oxidase ◽  
Normal Subjects ◽  
Human Platelets ◽  
Aggregation Response ◽  
Platelet Mao ◽  
Mao Activity ◽  
Platelet Mao Activity ◽  
Platelet Monoamine Oxidase ◽  
Induced Aggregation

SummaryPlatelet MAO activity and the aggregation response to epinephrine, ADP, and collagen were measured in normal subjects. There was a direct correlation between the amount of platelet MAO activity and the per cent aggregation induced by 1 and 2 μM epinephrine. There were lesser correlations between platelet MAO and ADP or collagen-induced aggregation. These findings suggest that platelet MAO may play a role in determining the response of human platelets to epinephrine.

Potentiation by α and Inhibition by β-Adrenergic Stimulations of Rat Platelet Aggregation

1977 ◽  
Vol 37 (03) ◽  
pp. 413-422 ◽  
Author(s):  
S. K Yu ◽  
J. G Latour
Keyword(s):  
Platelet Aggregation ◽  
Adrenergic Receptors ◽  
Inhibitory Effect ◽  
Human Platelets ◽  
Aggregation Response ◽  
Marked Inhibition ◽  
Potentiation Effect ◽  
Induced Aggregation ◽  
Rat Platelets ◽  
Stimulation Of

SummaryEpinephrine, known to potentiate and elicit aggregation of human platelets, was shown to inhibit thrombin-induced aggregation of rat platelets, delaying the onset of aggregation from 2 to 12 times. Incubation of rat platelet suspensions with propranolol (1.25–30 μM), inactive by itself, totally prevented the inhibitory effect of epinephrine and also permitted a potentiation effect to show up. On the contrary, phentolamine (1.25–30 μM) potentiated the inhibitory effect of epinephrine on rat platelets and unmasked an inhibitory effect on human platelets. Finally, isoproterenol (0.25–9 μM) produced a marked inhibition of aggregation induced by thrombin, ADP and collagen in the three species studied, but most particularly in the rat. From these results, we conclude that stimulation of the platelet adrenergic receptors may either result in promotion (α-stimulation) or inhibition (β-stimulation) of platelet aggregation. Furthermore, differences in the ratios or responses of α/β receptors may account for species variations in the platelet aggregation response to catecholamine challenge.

ATP- and ADP-Induced Rat Platelet Aggregation: Significance of Plasma in ATP-Induced Aggregation

1979 ◽  
Vol 42 (05) ◽  
pp. 1580-1588 ◽  
Author(s):  
Ethan J Haskel ◽  
Kailash C Agarwal ◽  
Robert E Parks
Keyword(s):  
Creatine Kinase ◽  
Platelet Aggregation ◽  
Human Plasma ◽  
Platelet Rich Plasma ◽  
Creatine Phosphate ◽  
Rat Plasma ◽  
Human Platelets ◽  
Induced Aggregation ◽  
Aggregation Of Platelets ◽  
Rat Platelets

SummaryATP caused platelet aggregation in rat platelet-rich plasma (PRP) but in contrast strongly inhibited ADP-induced human platelet aggregation. ADP-induced aggregation of rat platelets suspended in human plasma was strongly inhibited by ATP, whereas human platelets in rat plasma were aggregated by ADP. The ATP analog β,γ-methylene ATP which is not dephosphorylated did not induce aggregation in rat PRP. Adenosine, AMP, 2- chloroadenosine, α,β-methylene ADP and β,γ-methylene ATP each inhibited ATP-induced aggregation of platelets in rat PRP to a similar extent as ADP-induced aggregation. A solution containing creatine kinase and creatine phosphate (which converts ADP to ATP) rapidly reversed both ADP- and ATP-induced aggregation in rat PRP; preincubation with this solution completely inhibited rat platelet aggregation induced by both ADP and ATP. Adenosine-8-14C-triphosphate ([14C]-ATP) conversion to [14C]-ADP was about five-fold faster in rat plasma than in human plasma. Addition of creatine phosphate to rat PRP strongly inhibited ATP-induced aggregation, while creatine or creatine kinase slightly potentiated aggregation by ATP. Creatine phosphate, creatine, or creatine kinase individually had minimal and varying effects on ADP-induced rat platelet aggregation. These results suggest that the observed phenomenon of ATP-induced aggregation in rat PRP is caused by a higher activity of creatine kinase in rat plasma than in human plasma, which converts the added ATP to ADP, a potent aggregator.

The Effect of Red Blood Cells on the ADP-induced Aggregation of Human Platelets in Flow Through Tubes

1990 ◽  
Vol 63 (01) ◽  
pp. 112-121 ◽  
Author(s):  
David N Bell ◽  
Samira Spain ◽  
Harry L Goldsmith
Keyword(s):  
Platelet Aggregation ◽  
Shear Rate ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Platelet Rich Plasma ◽  
Mean Transit Time ◽  
White Blood Cells ◽  
Aggregate Size ◽  
Human Platelets ◽  
Induced Aggregation

SummaryThe effect of red blood cells, rbc, and shear rate on the ADPinduced aggregation of platelets in whole blood, WB, flowing through polyethylene tubing was studied using a previously described technique (1). Effluent WB was collected into 0.5% glutaraldehyde and the red blood cells removed by centrifugation through Percoll. At 23°C the rate of single platelet aggregtion was upt to 9× greater in WB than previously found in platelet-rich plasma (2) at mean tube shear rates Ḡ = 41.9,335, and 1,920 s−1, and at both 0.2 and 1.0 µM ADP. At 0.2 pM ADP, the rate of aggregation was greatest at Ḡ = 41.9 s−1 over the first 1.7 s mean transit time through the flow tube, t, but decreased steadily with time. At Ḡ ≥335 s−1 the rate of aggregation increased between t = 1.7 and 8.6 s; however, aggregate size decreased with increasing shear rate. At 1.0 µM ADP, the initial rate of single platelet aggregation was still highest at Ḡ = 41.9 s1 where large aggregates up to several millimeters in diameter containing rbc formed by t = 43 s. At this ADP concentration, aggregate size was still limited at Ḡ ≥335 s−1 but the rate of single platelet aggregation was markedly greater than at 0.2 pM ADP. By t = 43 s, no single platelets remained and rbc were not incorporated into aggregates. Although aggregate size increased slowly, large aggregates eventually formed. White blood cells were not significantly incorporated into aggregates at any shear rate or ADP concentration. Since the present technique did not induce platelet thromboxane A2 formation or cause cell lysis, these experiments provide evidence for a purely mechanical effect of rbc in augmenting platelet aggregation in WB.

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