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S L Pfueller

Publications and source records attributed to S L Pfueller.

At least 37 records · Page 2Linked to original sources
PubMed1984

Platelets deficient in glycoprotein I have normal Fc receptor expression.

Platelet glycoprotein I (GPI) is known to be required for the interaction of platelets with ristocetin and factor VIII:von Willebrand factor (VIII:vWf). However, its role as Fc receptor is not clear. Some studies have shown that enzymatic removal of GPI destroys the ability of platelets to react with VIII:vWf but not their ability to bind Ig G (IgG). Others have shown that IgG immune complexes which block the Fc receptor also inhibit VIII:vWf interaction with platelets. This subject has been re-examined by testing the ability of platelets with reduced amounts of GPI to aggregate and undergo the release reaction in response to stimuli which act at the platelet Fc receptor. Platelets from two patients with Bernard-Soulier syndrome, congenitally deficient in GPI, both aggregated and released 14C-serotonin normally when exposed to latex particles coated with IgG. Levels of GPI were decreased experimentally in normal platelets by treating them with chymotrypsin. Platelets treated in this manner did not aggregate or release [14C]serotonin in response to ristocetin-VIII:vWf. They did, however, both aggregate and release when incubated with heat-aggregated IgG, antigen-antibody complexes or latex particles coated with IgG. Thus the presence of GPI is not a prerequisite for platelet stimulation via the Fc receptor.

Blood Platelets↗
PubMed1984

Retraction.

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Retraction Notice↗
PubMed1983

Association of increased immune complexes, platelet IgG and serum IgG in chronic active hepatitis.

Platelet associated IgG (PA-IgG), serum IgG and immune complexes (IC) were measured and correlated with the degree of thrombocytopenia in 32 patients with chronic active hepatitis (CAH), classified as of autoimmune type in 24 and cryptogenic in eight. Of the 32 patients, 24 had raised PA-IgG and 18 of these were thrombocytopenic (greater than 150 X 10(9) platelets/1); in only two thrombocytopenic patients was the level of PA-IgG not increased. Platelet counts showed a significant inverse logarithmic correlation with PA-IgG levels (r = 0.456, P less than 0.01). Twelve patients had raised levels in serum of ICs, 11 of these also had raised PA-IgG and 10 of these 11 were thrombocytopenic. Serum IgG was raised in 10 patients and correlated with PA-IgG (r = 0.489, P less than 0.01). Of the 24 patients with autoimmune CAH, 13 had low platelet counts and 10 had raised levels of PA-IgG whereas of the eight patients with cryptogenic CAH, seven had raised PA-IgG and all were thrombocytopenic. These results for patients with CAH show that raised levels of circulating ICs are associated both with thrombocytopenia and with raised PA-IgG, and support the hypothesis that serum IgG and/or ICs may influence amounts of PA-IgG.

Antigen-Antibody Complex↗
PubMed1981

Relationship of raised platelet IgG in thrombocytopenia to total platelet protein content.

Platelet-associated IgG (PA IgG) of washed platelets of 20 normal controls and 45 thrombocytopenic patients was measured by radioimmunoassay and related to total platelet protein content. Mean values (+/- 2 SD) for 20 normals were 4.4 +/- 3.5 fg IgG per platelet (fg IgG/pl), 2.1 +/= 1.0 pg protein per platelet (pg protein/pl) and a ratio of IgG per g platelet protein of 2.1 +/- 1.8 mg IgG/g protein. Patients could be divided into two groups: Group I (31) with normal IgG/g protein ratios and either normal (16) or raised (15) fg IgG/pl, and Group II (14) with both fg IgG/pl and IgG/g protein raised. Of the 21 patients with idiopathic thrombocytopenia (ITP), 13 were in Group I (seven with raised and six with normal fg IgG/pl), and eight in Group II. There was significant correlation between PA IgG (fg IgG/pl) and platelet protein for the entire Group I (r = 0.95, P less than 0.001). The ITP patients in this group showed a similar correlation (r = 0.77, P less than 0.001), suggesting that raised PA IgG levels in Group I patients may be a result of protein-rich platelets. 60-90% of PA IgG was found in the soluble fraction of lysates of platelets from both normals and patients. Thus, it is either non-specifically associated with platelets or is antibody directed towards easily solubilized platelet antigens. Nine thrombocytopenic patients without immune disorders had raised PA IgG. These results question the assumption that raised PA IgG always indicates specific antiplatelet antibody.

Blood Platelets↗
PubMed1981

Quinine- and quinidine-dependent antiplatelet antibodies. Requirement of factor VIII-related antigen for platelet damage and for in vitro transformation of lymphocytes from patients with drug-induced thrombocytopenia.

The requirement of Factor VIII-related antigen (VIIIR:Ag) for platelet damage by quinine-and quinidine-dependent antibodies was studied in platelet-rich plasma (PRP) of four patients with severe von Willebrand's disease (vWd) (Factor VIII deficiency). Platelet factor 3 availability, platelet aggregation, and release of [(14)C]serotonin from labeled vWd-PRP by drug-dependent antibodies were significantly reduced in comparison with PRP from normal controls. Addition of purified VIIIR:Ag restored levels of platelet damage to that of normal PRP. In vWd-PRP, platelet damage by two human antiplatelet sera, not dependent on drugs, and by a rabbit antiplatelet serum did not differ from that in normal PRP. PRP from patients deficient in Factor VIII coagulant activity, Factor IX, or Factors II, VII, IX, and X behaved like normal PRP. The role of VIIIR:Ag in forming antigen able to transform lymphocytes of patients who had recovered from drug-induced thrombocytopenia was investigated by measuring incorporation of [methyl-(3)H]thymidine into DNA. When lymphocytes were cultured for 7 d, significantly less transformation occurred in response to platelets and the drug in the presence of vWd sera than in normal sera or sera deficient only in Factor VIII coagulant activity or Factor IX. Addition of purified VIIIR:Ag to vWd sera restored transformation to that obtained in normal sera. Nonspecific lymphocyte transformation by pokeweed mitogen was not affected by VIIIR:Ag. Thus VIIIR:Ag is involved both in platelet damage by drug-dependent antibodies and in the interaction between platelet and drug which produces an antigen able to transform sensitized lymphocytes.

Autoantibodies↗
PubMed1980

Study of the factors that cause specific transformation in cultures of lymphocytes from patients with quinine- and quinidine-induced immune thrombocytopenia.

Quinine- or quinidine-induced thrombocytopenic purpura is caused by synthesis of an immunoglobulin (Ig)G antibody, which caused platelet damage in the presence of the offending drug. The nature of the antigenic stimulus has been examined by measuring incorporation of [3H]thymidine into DNA during lymphocyte transformation to blast cells in the presence of the drug. Although patients' lymphocytes responded normally to the nonspecific mitogen, phytohemagglutinin P, they did not respond to either drug or platelets alone. However, significant transformation occurred when patients' lymphocytes were cultured for 7 d with homologous or autologous platelets in the presence of therapeutic concentrations of the drugs (0.39-39 microM). Platelet membranes were more active than intact platelets on the basis of protein content, whereas platelets from a patient with Bernard-Soulier syndrome were inactive. Washed platelets pretreated with the drugs were inactive when cultured with lymphocytes in the absence of the drugs, whereas platelets pretreated similarly in plasma caused transformation. Control lymphocytes from 20 normal patients and 6 patients with nondrug-induced thrombocytopenia were not transformed by drugs and platelets in the presence of normal serum or serum containing drug-dependent antibody, showing that the observed response was specific for presensitized lymphocytes. Thus lymphocytes of patients with drug-induced thrombocytopenia are transformed by an antigen that forms after interaction of plasma, specific platelet membrane components and the drug.

Antigen-Antibody Complex↗
PubMed1977

A comparative study of the effect of modification of the surface of human platelets on the receptors for aggregated immunoglobulins and for ristocentin-von Willebrand factor.

The receptors for aggregated immunoglobulin G (IgG) (an Fc receptor) and for ristocetin-von Willebrand factor on human platelets were studied by means of various modifications of the platelet surface. The expression of these receptors was measured by the agglutination of platelets to ristocetin in the presence of von Willebrand factor, which is part of the factor VIII complex, and by the binding of aggregated IgG coupled to 3H-labelled diazobenzene. Treatment of platelets with chymotrypsin, trypsin, papain and pronase which removed protein and glycoprotein from the platelet under conditions where the release reaction was inhibited caused loss of the expression of the receptor for ristocetin-von Willebrand factor and an enhancement of that for aggregated IgG. Induction of membrane changes with ADP and of the release reaction with the ionophore A23187 abolished agglutination to ristocentin-von Willebrand factor but did not alter the receptor for aggregated IgC. Possible contributions of unspecific membrane changes, produced by protease treatment of platelets, to the modification of receptor expression were eliminated by the use of formaldehyde-treated platelets. Trypsin, papain and pronase destroyed the ability of these platelets to agglutinate to ristocetin-von Willebrand factor but produced no change in the binding of aggregated IgC. Therefore, the receptor for ristocetin-von Willebrand factor is truly sensitive to proteolysis while the Fc receptor is not, but is partially masked by protease-sensitive material.

Adenosine Diphosphate↗
PubMed1977

Isolation of the membrane glycoproteins of human blood platelets by lectin affinity chromatography.

The major platelet membrane glycoproteins have been solubilized in 1.0% sodium deoxycholate and subjected to affinity chromatography on the lectins from Lens culinaris, wheat germ and Abrus precatorius. Polyacrylamide gel electrophoresis in the presence and absence of a reducing agent together with the differential binding of the lectins to the glycoproteins permitted the distinction of at least seven separate glycoprotein entities. A new nomenclature for the glycoproteins is proposed to accomodate the additional data. Using combinations of lectin columns, glycoproteins Ia and Ib could be prepared in a pure state and IIb and IIIa could be greatly purified. The binding of lectins to glycoprotein Ib has been strongly implicated as a necessary step in the aggregation response of platelets to lectins.

Blood Platelets↗
PubMed1977

Studies of the mechanism of the human platelet release reaction induced by immunologic stimuli. III. Relationship between the binding of soluble IgG aggregates to the Fc receptor and cell response in the presence and absence of plasma.

Aggregated IgG coupled covalently with bis-diazobenzidine (BDB-IgG) and labeled with 3H-diazobenzene (3H-BDB-IgG) has been used to study the binding of soluble IgG aggregates to human platelets in relationship to the release of the contents of intracellular granules (e.g., serotonin). In washed cell suspensions a minimum of 0.14 to 0.2 mug 3H-BDB-IgG per 5 X 10(8) platelets (40 to 70 aggregates per cell) was required for the triggering of the release reaction and cell aggregation. Binding was independent of divalent cations. The Arrhenius plot gave a straight line between 0 to 37 degrees C and a Q10 of 1.6. Neither inhibitors of the release reaction nor energy metabolism, nor formaldehyde fixation of the platelets affected binding. Bound 3H-BDB-IgG was not significantly eluted by IgG, bovine albumin (BSA), buffer, or plasma. Binding to washed platelets was more strongly inhibited by human IgG than by F(ab')2, bovine IgG, human albumin (HSA), or BSA. Plasma was an even more effective inhibitor of both binding and release. Plasma deficient in IgG or depleted of complement retained its inhibitory capacity. In the presence of plasma, at physiologic ratios of plasma and platelets, no release of serotonin was observed. Binding, although inhibited in rate, nevertheless occurred. It was enhanced by divalent cation chelation and had a Q10 of 2.5. The release reaction of washed platelets to which 3H-BDB-IgG had been bound in the presence of HSA or BSA was also inhibited by the subsequent addition of plasma or plasma proteins (human IgG being more effective than bovine IgG, F(ab')2, HSA, or BSA). 3H-BDB-IgG bound in the presence of either plasma or human IgG did not induce release when the platelets were subsequently suspended in media lacking these proteins. Thus, it appears that the platelet Fc receptor binds 3H-BDB-IgG by a process which is effectively inhibited by plasma, or by free IgG with an intact Fc, and to some extent by high concentrations of other proteins. The effects of bound IgG aggregates are dependent on the other proteins present both during binding and subsequently added. The mechanism of such receptor modulation and its implications in vivo are discussed.

Antigen-Antibody Complex↗