Biomedical subjects

E F Plow

Publications and source records attributed to E F Plow.

At least 163 records · Page 9Linked to original sources

PubMed1987

New mechanism for foam cell generation in atherosclerotic lesions.

Because of a close association between platelets and macrophages in early fatty streak lesions, the hypothesis was tested that platelets contribute to lesion progression by directly enhancing macrophage cholesteryl ester (CE) accumulation. Both the rate of cholesterol esterification and the accumulation of CE were increased within 24 h of the co-culture of adherent macrophages with platelets. Maximum increases in esterification and CE accumulation were observed within 3 to 4 d of culture and were greater than 10-fold over controls. Optimum accumulation of CE by 5 X 10(5) was obtained with 5 X 10(8) autologous platelets. When similar amounts of free cholesterol were supplied with platelets, red blood cells (RBC), RBC ghosts, or sonicated RBC, only platelets enhanced macrophage CE accumulation, which indicates specificity for platelets. Products released from platelets 30 min after thrombin stimulation were active as well. The results suggest that platelets and/or substances shed by activated platelets are potent mediators of macrophage CE accumulation.

Apolipoproteins E↗

PubMed1987

Divalent cation-dependent and independent surface expression of thrombospondin on thrombin-stimulated human platelets.

Thrombospondin (TSP), a platelet alpha-granule protein, becomes expressed on the surface of thrombin-stimulated platelets. The surface expression of this protein occurs through two distinct mechanisms. At low platelet concentrations (1 X 10(8)/mL), a divalent ion-dependent, low-capacity mechanism predominates. At higher cell concentrations, a divalent ion-dependent, higher capacity mechanism prevails that can account for greater than 90% of all the TSP surface expression measured. This mechanism requires the presence of both calcium and magnesium (Ca + Mg). The dependence of the divalent ion-dependent surface expression on platelet concentration suggests that release of the molecule from the cell followed by its binding to the cell surface mediates this component of the endogenous TSP-platelet interaction. These data are consistent with a two-receptor model for the platelet-surface expression of the endogenous TSP pool.

Alprostadil↗

PubMed1987

Arginyl-glycyl-aspartic acid sequences and fibrinogen binding to platelets.

Human fibrinogen has an Arg-Gly-Asp-Ser (RGDS) sequence at residues 572-575 of its A alpha-chain. Although RGDS-containing peptides inhibit fibrinogen binding to stimulated platelets, these peptides also inhibit platelet binding of human fibrinogen fragment X and rat fibrinogen, which lack RGDS sequences corresponding to A alpha 572-575. Thus competition between free RGD-containing peptides and internal RGDS sequence at A alpha 572-575 is not the basis for their inhibition of fibrinogen binding to platelets. Addition of a Thr to the carboxy-terminus and an Asn to the amino-terminus of the RGDS sequence, the amino acids corresponding to A alpha 576 and 571 respectively, reduced the inhibitory potency of RGDS-containing peptides by fourfold to tenfold. Arg-Gly-Asp-Phe (RGDF) corresponds to A alpha 95-98, and the RGDF peptide was an effective inhibitor of fibrinogen binding, fourfold to fivefold more potent than RGDS. Thus, local primary structure may play an important role in regulating the capacity of RGD sequences in proteins to interact with specific adhesion receptors.

Adenosine Diphosphate↗

PubMed1987

Increased surface expression of the membrane glycoprotein IIb/IIIa complex induced by platelet activation. Relationship to the binding of fibrinogen and platelet aggregation.

Platelet activation altered the binding of three monoclonal antibodies (monovalent Fab' fragment) directed against the glycoprotein (GP) IIb/IIIa complex. An increased binding of two- to threefold occurred after stimulation with thrombin or phorbol myristate acetate (PMA), with slight but significant increase in the dissociation constants (Kd) of two antibodies (LJ-CP8 and LJ-P9). In contrast, no statistically significant changes were observed with ADP-stimulated platelets. The increased binding of LJ-CP3, but not of the other two antibodies, to activated platelets decreased by 30% to 40% in the presence of EDTA at 22 to 25 degrees C. Platelets stimulated by thrombin or PMA bound more fibrinogen than did those stimulated by ADP, and significant differences in the extent but not in the affinity of fibrinogen binding were observed with various platelet agonists. When the pool of GP IIb/IIIa molecules exposed on the surface of unstimulated platelets was reacted with the monoclonal antibody LJ-CP3 to block ADP-induced fibrinogen binding and platelet aggregation, stimulation with thrombin or PMA still induced substantial binding of antibody and fibrinogen, and aggregation ensued. Therefore, platelets exposed to "strong" agonists exhibit an increased number of surface-oriented epitopes associated with GP IIb/IIIa. The GP IIb/IIIa molecules bearing these newly exposed epitopes are functional in that they can bind fibrinogen and mediate platelet aggregation.

Antibodies, Monoclonal↗

PubMed1986

Topography of the high-affinity lysine binding site of plasminogen as defined with a specific antibody probe.

An antibody population that reacted with the high-affinity lysine binding site of human plasminogen was elicited by immunizing rabbits with an elastase degradation product containing kringles 1-3 (EDP I). This antibody was immunopurified by affinity chromatography on plasminogen-Sepharose and elution with 0.2 M 6-aminohexanoic acid. The eluted antibodies bound [125I]EDP I, [125I]Glu-plasminogen, and [125I]Lys-plasminogen in radioimmunoassays, and binding of each ligand was at least 99% inhibited by 0.2 M 6-aminohexanoic acid. The concentrations for 50% inhibition of [125I]EDP I binding by tranexamic acid, 6-aminohexanoic acid, and lysine were 2.6, 46, and 1730 microM, respectively. Similar values were obtained with plasminogen and suggested that an unoccupied high-affinity lysine binding site was required for antibody recognition. The antiserum reacted exclusively with plasminogen derivatives containing the EDP I region (EDP I, Glu-plasminogen, Lys-plasminogen, and the plasmin heavy chain) and did not react with those lacking an EDP I region [miniplasminogen, the plasmin light chain or EDP II (kringle 4)] or with tissue plasminogen activator or prothrombin, which also contain kringles. By immunoblotting analyses, a chymotryptic degradation product of Mr 20,000 was derived from EDP I that retained reactivity with the antibody. The high-affinity lysine binding site was equally available to the antibody probe in Glu- and Lys-plasminogen and also appeared to be unoccupied in the plasmin-alpha 2-antiplasmin complex. alpha 2-Antiplasmin inhibited the binding of radiolabeled EDP I, Glu-plasminogen, or Lys-plasminogen by the antiserum, suggesting that the recognized site is involved in the noncovalent interaction of the inhibitor with plasminogen.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies↗

PubMed1986

Lymphocyte suppressive peptides from fibrinogen are derived predominantly from the A alpha chain.

Cellular immune responses can elicit local deposition of fibrin at the site of immunologic reactions, as well as the formation of intravascular fibrin in disseminated reactions. The subsequent physiologic proteolysis of fibrinogen and fibrin by plasmin results in small peptides that suppress lymphocyte functions in vitro and in the immune response in vivo. The intramolecular origin of lymphocyte suppressive activity and the proteolytic events responsible for the release of active peptides have been analyzed. Plasmic peptides from the isolated B beta and gamma constituent chains of fibrinogen did not inhibit mitogen-driven responses of human peripheral blood mononuclear cells. In contrast, plasmic digests of the A alpha chain, but not the intact A alpha chain were suppressive. Advanced plasmic digests of fibrinogen and the A alpha chain were suppressive at similar concentrations, suggesting that biological activity is derived predominantly from the A alpha chain. Limited plasmic digests of fibrinogen were fractionated to yield a heat-precipitable 250,000 dalton fragment X and heat-soluble proteolytic products containing fragments derived from the carboxyl-terminal region of the A alpha chain including a 42,000 dalton major A alpha chain derivative. Neither fragment X nor derivatives produced by its additional plasmic proteolysis were suppressive. In contrast, the heat-soluble fraction from limited plasmic cleavage was suppressive, and this activity was enhanced 10-fold by additional plasmic cleavage of this fraction. The isolated 42,000 dalton A alpha chain fragment was devoid of activity, but plasmic digestion of this derivative generated peptides of less than 8000 daltons that inhibited mitogen-stimulated thymidine uptake by lymphocytes. Two synthetic peptides corresponding to A alpha 220-230 and B beta 43-47, peptides with known vasoactive activities, suppressed lymphocyte thymidine uptake at very high concentrations. Based on their maximal yield from plasmic digests of fibrinogen, these two peptides would account for only 1% of the immunosuppressive activity of fibrinogen derivatives. In summary, the results indicate that the suppressive activity of fibrinogen is predominantly derived from the 42,000 dalton carboxyl terminal region of the A alpha chain of the molecule and is not attributable to the known vasoactive peptides. Initial proteolytic release of this region from the core of fibrinogen does not result in suppressive activity, but additional cleavage releases small peptides with the lymphocyte inhibitory function.

Fibrin↗

PubMed1986

Expression of intracellular fibrinogen on the surface of stimulated platelets.

Participation of fibrinogen in platelet aggregation is contingent upon the capacity of various stimuli to induce specific receptors for the molecule on the surface of the cell. The interaction of fibrinogen with this receptor results directly in platelet aggregation, and dissociation of fibrinogen is associated with disaggregation. While the role of exogenous fibrinogen in this process has been fully documented, the mechanisms which control the surface exposure of platelet fibrinogen are less understood. In the present study Fab fragments of antibodies monospecific for fibrinogen have been used to examine the surface expression of intracellular fibrinogen and its involvement in platelet aggregation. Radiolabelled Fab fragments did not interact with non-stimulated platelets but significant binding was observed when the cells were stimulated by ADP, thrombin, collagen and Ca ionophore A23187. Binding was specific for fibrinogen, was not observed with thrombasthenic platelets and was dependent upon the presence of extracellular calcium. With all stimuli tested, the binding of the Fab probe to platelets correlated with platelet secretion. At the following concentrations of stimuli: 30 microM ADP, 4 micrograms/ml collagen, 3 microM A23187 and 0.05 U/ml thrombin, the immune Fab fragments inhibited platelet aggregation. A monoclonal antibody to glycoprotein IIb/IIIa complex and a synthetic peptide gamma 400-411, that inhibited the interaction of plasma fibrinogen with platelets, did not inhibit the binding of 125I-FAB fragments. Taken together these results support the hypothesis that endogenous fibrinogen becomes surface-expressed during stimulation of the cell and can support platelet aggregation, particularly that induced by low concentrations of stimuli. The mechanism for the surface expression of platelet fibrinogen may be distinct from that for the binding of plasma fibrinogen.

Antibody Specificity↗

PubMed1986

Interaction of thrombospondin with resting and stimulated human platelets.

The interaction of isolated and radioiodinated thrombospondin with washed human platelets has been characterized. The ligand bound to nonstimulated and thrombin-stimulated platelets in a time-dependent manner, and apparent steady state was reached within 25 min. Binding was not due to iodination of the ligand and was inhibited by nonlabeled thrombospondin but not by unrelated proteins, and bound ligand was identical with thrombospondin in terms of subunit structure. Nonlinear curve-fitting analyses of binding to resting platelets suggested the presence of a single class of sites which bound 3,100 +/- 1,000 molecules/platelet with an apparent Kd of 50 +/- 20 nM. This interaction was not attributable to contaminating cells or inadvertant platelet activation. Binding to thrombin-stimulated platelets had a lower apparent affinity (Kd = 250 +/- 100 nM) and higher apparent capacity (35,600 +/- 9,600 molecules/platelet). Thrombin-enhanced binding was dependent upon agonist dose and platelet stimulation. Fibrinogen, a monoclonal antibody to GPIIb-IIIa, temperature, and divalent ions had differential effects upon thrombospondin binding to resting and stimulated platelets, suggesting the presence of two distinct mechanisms of thrombospondin binding to platelets. While thrombospondin binding to thrombin-stimulated platelets occurs with characteristics similar to those observed for fibrinogen, fibronectin, and von Willebrand Factor, its high affinity interaction with resting platelets is unique to this adhesive glycoprotein.

Binding, Competitive↗

PubMed1986

Polymorphism of platelet glycoprotein Ib in the United States.

Platelet glycoprotein (GP) Ib from healthy individuals from the United States was analyzed using SDS-polyacrylamide gel electrophoresis and staining with peanut agglutinin-coupled peroxidase or wheat germ agglutinin-coupled peroxidase after transfer of electrophoresed proteins to nitrocellulose. The GPIb from American Caucasians (109 individuals) was found to be polymorphic, showing types A, B, C, and D of GPIb, similar to what was observed in Japanese. The phenotype distribution pattern, however, was very different from that observed in the Japanese population. GPIb heterogeneity was also observed in American Blacks, Asian Americans, and Americans of Hispanic origin. Thus, it appears that the polymorphism of GPIb is a general phenomenon which should be regarded as an important factor when doing studies on this glycoprotein.

Asian People↗

PubMed1986

Platelet membrane glycoprotein IIb/IIIa: member of a family of Arg-Gly-Asp--specific adhesion receptors.

Adhesive interactions of the platelet surface with plasma proteins such as fibrinogen and fibronectin play an important role in thrombosis and hemostasis. The binding of both of these proteins to platelets is inhibited by synthetic peptides containing the sequence Arg-Gly-Asp, which corresponds to the cell adhesion site in fibronectin and is also present in the alpha chain of fibrinogen. An affinity matrix made of an insolubilized heptapeptide containing the Arg-Gly-Asp sequence selectively binds the platelet membrane glycoprotein IIb/IIIa from detergent extracts of platelets. When incorporated into liposome membranes, the isolated protein confers to the liposomes the ability to bind to surfaces coated with fibrinogen, fibronectin, and vitronectin but not to surfaces coated with thrombospondin or albumin. This platelet receptor is related to the previously identified fibronectin and vitronectin receptors in that it recognizes an Arg-Gly-Asp sequence but differs from the other receptors in its wider specificity toward various adhesive proteins. These results establish the existence of a family of adhesion receptors that recognize the sequence Arg-Gly-Asp.

Amino Acid Sequence↗

PubMed1986

Specific association of thrombin-antithrombin complexes with a human hepatoma cell line.

The clearance of thrombin-antithrombin (TAT) complexes from blood by the liver is through a receptor mediated pathway. We have used the established human hepatoma cell line, Hep G2, to determine if these hepatocytes have the capacity to bind this enzyme-inhibitor complex. The TAT complex was bound to the cells in a time and temperature dependent manner, reaching an apparent steady state at 90 minutes at both 4 and 37 degrees C. Binding at 4 degrees C was 5-7-fold less extensive than at 37 degrees C. The bound TAT was structurally similar to the added ligand. This interaction was specific, as it was inhibited by nonlabeled TAT but not by 50-fold molar excesses of unrelated proteins or by the individual constituents, thrombin or antithrombin. Factor Xa- antithrombin complex inhibited the binding reactions slightly. Specific binding isotherms at 37 degrees C were subjected to Scatchard plots. The apparent dissociation constant was 247 +/- 74 nM, and the number of TAT molecules bound per cell was 5.19 +/- 0.89 X 10(5). Bound TAT complexes did not undergo degradation at 4 or 37 degrees C for up to 2.5 hr, as greater than 85% of the bound ligand was acid precipitable during the time course of binding. Internalization of the TAT complex was compared with transferrin, a molecule known to be internalized by Hep G2 cells, by resistance of the cell-bound ligands to degradation by trypsin or pronase. In contrast to transferrin, most of the TAT complexes remained cell-surface associated for at least 2 hr at both 4 degrees and 37 degrees C, indicating that TAT was not substantially internalized by the Hep G2 cells.

Antithrombins↗

PubMed1986

The contribution of leukocyte proteases to fibrinolysis.

Polymorphonuclear leukocytes accumulate within blood clots and may contribute to fibrinolysis. The primary fibrinolytic enzymes of neutrophils are cathepsin G and elastase. Fibrin can be exposed to these granular enzymes as a result of cell lysis, phagocytosis of fibrin, or secretion of the enzymes from the cells. Neutrophil secretion occurs in association with blood coagulation and is dependent upon a plasma factor(s) and calcium. After secretion, the enzymes can degrade fibrin within a plasma environment. This is demonstrated by the inhibition of fibrinolysis by specific inhibitors of elastase and the augmentation of fibrinolysis by neutralization of the primary plasma inhibitor of elastase, alpha 1-proteinase inhibitor. A radioimmunoassay which discriminates elastase from plasmic degradation products of fibrinogen has been developed. In this assay, elastase elicited degradation products of fibrin(ogen) were detected in certain pathophysiologic plasma samples. Taken together, these findings indicate a role for leukocyte proteases in physiological fibrinolysis.

Animals↗

PubMed1986

Immunologic relationship between platelet membrane glycoprotein GPIIb/IIIa and cell surface molecules expressed by a variety of cells.

A polyclonal antiserum to platelet membrane glycoprotein GPIIb/IIIa was used to detect antigenically related molecules on a diverse panel of human cells. Umbilical vein endothelial cells, erythroleukemic HEL cells, and diploid fetal lung GM1380 fibroblasts expressed GPIIb/IIIa-related molecules, as judged by immunofluorescence and immunoprecipitation of surface-labeled proteins. The GPIIb and GPIIIa subunits were both present and were of similar molecular weight in these cell types. These molecules were synthetic products of the cells, as shown by immunoprecipitation of intrinsically labeled proteins. Promyeloid U937 cells could be induced by 4 beta-phorbol 12-myristate 13-acetate to synthesize and express GPIIb/IIIa-related molecules on their cell surface. The GPIIb/IIIa-related molecules were not precisely identical in the various cell types, based on slight differences in electrophoretic mobility and their failure to react with monoclonal antibodies specific for each subunit of platelet GPIIb/IIIa. These results suggest the existence of a widely distributed family of GPIIb/IIIa-related molecules. This family of "cytoadhesins" may share a common function in cellular adhesive reactions.

Antibodies, Monoclonal↗

PubMed1986

The plasminogen system and cell surfaces: evidence for plasminogen and urokinase receptors on the same cell type.

The capacity of cells to interact with the plasminogen activator, urokinase, and the zymogen, plasminogen, was assessed using the promyeloid leukemic U937 cell line and the diploid fetal lung GM1380 fibroblast cell line. Urokinase bound to both cell lines in a time-dependent, specific, and saturable manner (Kd = 0.8-2.0 nM). An active catalytic site was not required for urokinase binding to the cells, and 55,000-mol-wt urokinase was selectively recognized. Plasminogen also bound to the two cell lines in a specific and saturable manner. This interaction occurred with a Kd of 0.8-0.9 microM and was of very high capacity (1.6-3.1 X 10(7) molecules bound/cell). The interaction of plasminogen with both cell types was partially sensitive to trypsinization of the cells and required an unoccupied high affinity lysine-binding site in the ligand. When plasminogen was added to the GM1380 cells, a line with high intrinsic plasminogen activator activity, the bound ligand was comprised of both plasminogen and plasmin. Urokinase, in catalytically active or inactive form, enhanced plasminogen binding to the two cell lines by 1.4-3.3-fold. Plasmin was the predominant form of the bound ligand when active urokinase was added, and preformed plasmin can also bind directly to the cells. Plasmin on the cell surface was also protected from its primary inhibitor, alpha 2-antiplasmin. These results indicate that the two cell lines possess specific binding sites for plasminogen and urokinase, and a family of widely distributed cellular receptors for these components may be considered. Endogenous or exogenous plasminogen activators can generate plasmin on cell surfaces, and such activation may provide a mechanism for arming cell surfaces with the broad proteolytic activity of this enzyme.

Cell Line↗

PubMed1986

Plasminogen interacts with human platelets through two distinct mechanisms.

Glu-plasminogen, the native form of plasminogen, interacts in a specific and saturable manner with unstimulated human platelets, and the binding is enhanced fivefold by thrombin stimulation (Miles and Plow, 1985. J. Biol. Chem. 260:4303). This study characterizes the nature of the Glu-plasminogen binding sites by analyzing platelets deficient in selected proteins and functions. Platelets from patients with afibrinogenemia, Gray platelet syndrome, and the Cam Variant of thrombasthenia, a form of thrombasthenia with near normal levels of glycoprotein IIb/IIIa (GPIIb/IIIa), showed minimal augmentation of plasminogen binding to thrombin-stimulated platelets but normal binding to unstimulated platelets. This selective deficiency indicates that two distinct mechanisms are involved in the interaction of plasminogen with platelets. These abnormal platelets share a deficiency in fibrinogen. Surface expression of platelet fibrinogen, however, was not sufficient for enhanced plasminogen binding to stimulated platelets, and experiments with alpha-thrombin and gamma-thrombin indicated that fibrin formation on the platelet surface is necessary for the augmented plasminogen binding. Unstimulated and stimulated thrombasthenic platelets deficient in GPIIb/IIIa bound markedly reduced levels of plasminogen, which suggests a role for GPIIb/IIIa in plasminogen binding to unstimulated platelets. Treatment of platelets to dissociate the heterodimeric complex of GPIIb/IIIa did not significantly perturb plasminogen binding to unstimulated platelets, but the complex may be necessary for thrombin-stimulated plasminogen binding via its interaction with platelet fibrin.

Blood Platelets↗

PubMed1986

Divalent cation regulation of the surface orientation of platelet membrane glycoprotein IIb. Correlation with fibrinogen binding function and definition of a novel variant of Glanzmann's thrombasthenia.

An antiplatelet monoclonal antibody, PMI-1, reacts with glycoproteins (GP) GPIIb, free GPIIb, and the GPIIb-IIIa complex. This antibody binds to 40,900 sites per platelet, with a Kd = 0.95 microM, and its binding is inhibited by the presence of magnesium or calcium in the suspending medium (50% suppression at approximately 0.5 mM divalent cation). Regulation of the PMI-1 epitope is independent of disassembly of the GPIIb-IIIa heterodimer, because it occurred at 22 degrees C and in response to mM magnesium as well as calcium. PMI-1 binding inversely correlated with fibrinogen binding. In addition, we identified a variant of Glanzmann's thrombasthenia with near-normal platelet content of the GPIIb-IIIa heterodimer as judged by crossed immunoelectrophoresis and surface labeling. Binding of PMI-1 to these patients' platelets was not dependent on reduction of the divalent cation concentration. These data suggest that the surface orientation of GPIIb is important in the capacity of platelets to bind fibrinogen.

Antibodies, Monoclonal↗

PubMed1986

Identification of a new class of inducible receptors on platelets. Thrombospondin interacts with platelets via a GPIIb-IIIa-independent mechanism.

Thrombospondin with fibrinogen, fibronectin, and von Willebrand factor binds to platelets stimulated with agonists and support platelet adhesive functions. The receptors for the latter three proteins are associated with membrane glycoprotein GPIIb-IIIa. Thrombasthenic platelets deficient in GPIIb-IIIa have been utilized to examine the role of this membrane protein in the interactions of thrombospondin with platelets. Radioiodinated thrombospondin bound to thrombin-stimulated platelets from normal and thrombasthenic donors with a similar affinity and capacity. As monitored with a monoclonal antibody to thrombospondin, the divalent ion-dependent and -independent pathways for the expression of the endogenous pool of thrombospondin on the surface of thrombin-stimulated platelets from normal and thrombasthenic donors were also qualitatively and quantitatively similar. GPIIb-IIIa or ligands associated with GPIIb-IIIa thus are not essential for the binding of thrombospondin to platelets. Therefore, thrombospondin interacts with unique receptors on platelets.

Antibodies, Monoclonal↗

PubMed1986

Localization of internal pools of membrane glycoproteins involved in platelet adhesive responses.

To investigate the existence of intracellular pools of membrane glycoproteins involved in platelet adhesive reactions, the authors have studied the distribution of glycoprotein (GP) Ib and IIb/IIIa by immunofluorescence and immunoelectron microscopy. Studies on whole cells and frozen thick sections revealed a rim pattern of fluorescence for GPIb and GPIIb/IIIa consistent with a surface distribution. In addition, extensive staining occupying the entire cell interior was observed for anti-GPIIb/IIIa, whereas anti-GPIb revealed staining of large intracellular structures that contained no stainable fibrinogen. On the ultrastructural level, the extracellular face of the plasma membrane and the intraluminal face of vacuolar structures were stained with both anti-GPIb and anti-GPIIb/IIIa. Additionally, GPIIb/IIIa antigen was localized to alpha-granule membranes. To determine whether alpha-granule GPIIb/IIIa could be transported to the cell surface, the authors employed a calcium-dependent monoclonal anti-GPIIb/IIIa antibody. Incubation of platelets with EGTA at 37 C abolished staining of plasma membrane and vacuolar but not alpha-granule GPIIb/IIIa. Recalcification of these cells failed to restore the epitope; however, thrombin treatment of recalcified cells reconstituted surface staining with a concurrent loss of internal staining. These data suggest that GPIIb/IIIa is present in alpha-granule membranes and may be transported to the cell surface in response to thrombin treatment. In addition, both GPIb and GPIIb/IIIa antigens are present in intracellular membrane-bounded vacuolar structures which are closed to antibody probes in fixed cells. Redistribution of these internal pools of adhesive protein "receptors" may participate in the regulation of platelet adhesive properties.

Blood Platelets↗