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B A Fiedel

Publications and source records attributed to B A Fiedel.

34 records · Page 2Linked to original sources
PubMed1981

Platelet activating factor: an inhibitor of neutrophil activation?

Preparations of platelet activating factor (PAF) derived by methanolic extraction of supernatants from antigen-challenged rabbit basophils proved capable of activating platelets while concurrently inhibiting neutrophil aggregation/secretion stimulated by biologically active F-Met peptides, ionophore A23187, or zymosan-treated serum. This inhibition was non-cytotoxic and species-non-specific. When these PAF preparations were analysed using thin-layer chromatography, multiple lipids were detected. Both platelet-stimulating as well as neutrophil-inhibitory activity was present in a lipid component migrating at an RF consistent with native PAF; however, these biological activities were not limited only to PAF and, indeed, could also be detected in lipid with solubility characteristics more closely related to a lysophosphatide than to native PAF. These data are compatible with the belief that native PAF may belong to a family of biologically active lipids differing somewhat in physico-chemical properties. Moreover, these data illustrate that PAF and/or PAF-like molecules may also demonstrate a biological activity distinct from their effects upon the platelet.

Animals↗
PubMed1979

Inhibition of platelet aggregation by native and desialised alpha-1 acid glycoprotein.

The alpha-1 acid glycoprotein (orosomucoid; AAG) is a normal constituent of human plasma (650+/-215 microgram ml(-1)) which increases in concentration as much as fivefold in associations with acute inflammation and cancer, and thus is recognized as an acute phase protein. AAG consists of a single polypeptide chain, has a molecular weight of 44,100, and contains approximately 45% carbohydrate including 12% sialic acid; it is the most negatively charged of the plasma proteins. Certain of the biological properties of AAG are related to its sialic acid content; thus, clearance and immunogenicity of AAG are markedly increased on desialisation. The biological functions of AAG are largely unknown. AAG has the ability to inhibit certain lymphocyte re-activities including blastogenesis in response to concanavalin A, phytohaemagglutinin and allogeneic cells, and these inhibitory effects are enhanced in association with desialisation. In view of these observations, a report that unphysiologically large (5--15 mg ml(-1)) amounts of AAG inhibit the platelet aggregation induced by ADP and adrenaline, and evidence that a sialic acid-deficient species of AAG appears elevated in several chronic disease states, we compared the effects of AAG and its desialised counterpart (AAG-D) on platelet aggregation. We report that desialisation of AAG is associated with increased expression of activity inhibitory to the platelet aggregation otherwise observed on stimulation with ADP, collagen or thrombin.

Adenosine Diphosphate↗
PubMed1979

Modulation of platelet activation by native DNA.

Native DNA (dsDNA) was found to induce the aggregation of isolated human platelets and the release of platelet 5HT; this activation was inhibited by both theophylline and TYA, suggesting a role for cAMP and metabolic products formed from arachidonate. By contrast, nonaggregating amounts of dsDNA inhibited platelet activation induced by collagen or thrombin. This inhibition, which could be overcome by use of greater amounts of the stimulatory agents, was not associated with the loss of platelet viability. Activation of platelets by dsDNA was not observed in plasma or in isolated platelet systems to which small amounts of cell-free plasma were added. However, dsDNA maintained in plasma its ability to inhibit platelet aggregation induced by collagen and thrombin. RNA and single-stranded DNA failed to induce platelet aggregation or release of 5HT and to block the platelet activation stimulated by dsDNA. Further, dsDNA did not significantly inhibit platelet aggregation in platelet-rich plasma stimulated by ADP or epinephrine. These data implicate dsDNA as a selective and potentially important activator and modulator of platelet responsiveness.

Adenosine Diphosphate↗
PubMed1978

Activation of the alternative complement pathway by a streptococcal lipoteichoic acid.

A glycerol lipoteichoic acid antigen from Streptococcus pyogenes 1-RP41 was found by rabbit erythrocyte hemolytic assay to activate the alternative complement pathway in human sera. Over a narrow concentration range of the teichoic acid, complement consumption was dose dependent, whereas at higher concentrations of the acid complement consumption could not be detected.

Antigens, Bacterial↗
PubMed1978

Activation of human platelets by platelet activating factor (PAF) derived from sensitized rabbit basophils.

Rabbit basophil-derived platelet activating factor (PAF), a mediator of anaphylaxis, induces the aggregation and release of serotonin from rabbit platelets. In the present study, we report that PAF obtained by challenge of specifically sensitized rabbit basophils induced the noncytotoxic release of serotonin from human platelets; maximal extent of release ranged between 34-46%. This release was unaltered in the presence of indomethacin, indicating that such secretion was not a consequence of contaminating arachidonic acid; further, as previously demonstrated with platelets of rabbit origin, it was markedly independent of a requirement for an intact prostaglandin biosynthetic pathway. In contrast to its effect upon rabbit platelets, rabbit PAF did not induce aggregation of human platelets, suggesting that the aggregation and secretion reactions induced by this agent are separable and that this cross-species activation may be incomplete. Whether this is a result of the differential ability of rabbit PAF to bind to and activate rabbit as compared to human platelets or to the existence of a family of PAF molecules is not yet known. The capacity of PAF to participate in a secretory event involving human platelets lends support to the belief that PAF may play an important ubiquitous role in the cooperative, leucocyte-dependent, release of vasoactive amines which results in increased vascular permeability.

Animals↗
PubMed1977

Effects of C-reactive protein on platelet function. III. The role of cAMP, contractile elements, and prostaglandin metabolism in CRP-induced inhibition of platelet aggregation and secretion.

It was previously demonstrated that C-reactive protein (CRP) inhibits platelet aggregation and release reactions, activation of platelet factor 3, and platelet-dependent clot retraction. Multiple considerations including selective inhibition of secondary wave aggregation suggested that CRP exerted its inhibitory effects by interfering with the release of endogenous ADP. In the present investigation, CRP was found by direct assay to inhibit the release of endogenous ADP and/or serotonin concomitant with inhibition of platelet aggregation stimulated by ADP, epinephrine, thrombin, and AHGG. CRP did not induce an increase in the basal level of platelet cAMP, suggesting independence of a direct effect upon this mediator system. Furthermore, CRP did not inhibit the aggregation and secretion induced by the antibiotic ionophore A23187, suggesting the absence of a direct effect upon the activation of platelet contractile elements. By contrast, CRP did inhibit both thrombin-induced release of malondialdehyde, a prostaglandin endoperoxide nonprostanoate endproduct, and platelet aggregation induced by the prostaglandin endoperoxide precursor arachidonic acid. These data, therefore, raise the possibility that CRP inhibits platelet reactivities by interfering with an aspect of porstaglandin metabolism, and that this occurs subsequent to the hydrolytic accumulation of arachidonic acid and prior to the movement of calcium from the platelet dense tubules. These studies support the concept that CRP serves to modulate platelet reactivities during acute inflammatory reactions.

Adenosine Diphosphate↗
PubMed1976

Immunogenicity of a purified and carrier-complexed streptococcal lipoteichoic acid.

Solublie teichoic acid could not stimulate the formation of antibodies either as an aqueous solution or in an emulsion with Freund incomplete adjuvant. However, when given as precipitates with methylated bovine serum albumin, it stimulated strong anti-teichoic acid responses. High levels of anti-teichoic acid antibodies usually resulted in allergic symptoms upon secondary challenge either with immunogenic teichoic acid-methylated bovine albumin complexes or with non-immunogenic soluble teichoic acid. These symptoms suggested anaphylatic shock, but probably also included the formation of complement-consuming immune complexes.

Adjuvants, Immunologic↗
PubMed1976

Complement activation by interaction of polyanions and polycations.

Interactions between heparin and protamine in normal human serum previously were found to activate the primary complement pathway and deplete the early-acting complement components. In the present investigation, the role of heparin-protamine complexes, immunoglobulins, C1q and C1-INH in this interaction was studied. Heparin and protamine, like antibody and antigen, were found to combine in multiple proportions; those proportions which resulted in optimal precipitation also induced maximal C consumption. Complexes formed in serum contained C1q and IgG, but the amount of C1q was insufficient to account for the total depletion of C1 haemolytic activity, and immunoglobulins were not required for activation of complement to occur: maximal consumption was observed in immunoabsorbed hypogammaglobulinaemic sera in which IgG, IgM and IgA were undetectable (less than 5, less than 10 and less than 7 mug/ml, respectively). Purified C1q aggregated heparin-protamine complexes formed or forming in the presence or absence of serum. The ability to induce maximal C consumption was rapidly lost as heparin and protamine interacted, and complexes preformed either in serum or buffer, or supernates thereof, were relatively ineffective in complement consumption. Thus, the consumption of complement seems to occur via transient reactivity with C1,probably at the level of C1q. It seems to be limited by the ability of free heparin to potentiate the activity of C1-INH, and perhaps also by its direct effect upon the early acting C components. These experiments support the concept that complement activation by interactions between polyelectrolytes such as heparin and protamine, like interactions between the antibodies and antigens, may have a role in the initiation of inflammatory reactions by direct activation of the complement system.

Agammaglobulinemia↗
PubMed1976

Effects of C-reactive protein on platelet function. I. Inhibition of platelet aggregation and release reactions.

C-reactive protein (CRP) is an acute phase reactant which shares numerous functional characteristics with the immunoglobulins. In the present study CRP was found to inhibit the aggregation of human platelets stimulated by either modified human immunoglobulin or thrombin. This effect did not involve chelation of calcium or cytotoxicity, and was overcome by larger amounts of the aggregating agents. CRP also inhibited the activation but not the activity of platelet factor 3 and the release of beta-glucuronidase. Thus, CRP can inhibit multiple platelet reactivities. We suggest that this property of CRP may play an important role in the control of platelet responsiveness during reactions of inflammation, defense, and repair.

Blood Platelets↗
PubMed1976

Effects of C-reactive protein on platelet function. II. Inhibition by CRP of platelet reactivities stimulated by poly-L-lysine, ADP, epinephrine, and collagen.

It was recently demonstrated that C-reactive protein (CRP)4 inhibits the response of human platelets to heataggregated human gamma-globulin and thrombin and that this inhibition is characterized by a dose-dependent reduction in aggregation, activation of platelet factor 3 (PF3), and release of beta-glucuronidase. In the present experiments, CRP was found also to inhibit the ability of washed human platelets to aggregate in response to poly-L-lysine (PLL); in these experiments, the magnitude of the inhibitory effect was dependent upon the m.w. of PLL used as the stimulating agent, and was more effective with low (15,000 daltons) than with high (400,000 daltons) m.w. polymers. CRP similarly inhibited ADP- and epinephrine-stimulated platelet aggregation in platelet-rich plasma (PRP), and this was characterized by relatively minimal suppression of the primary wave of aggregation. CRP also inhibited the platelet aggregation induced by collagen in PRP, although it had no effect upon the adherence of platelets to collagen. Finally, CRP inhibited the activation of PF3 and the release of serotonin during stimulation of platelets with ADP, and this inhibition was temporally related to the onset of the secondary wave of aggregation. These experiments extend the platelet reactivities inhibited by CRP, show that CRP expresses its inhibitory capacity in platelet-rich plasma as well as upon isolated platelets, raise the possibility that CRP exercises its effects by inhibiting or interfering with the release and/or utilization of endogenous platelet ADP, and support the concept that CRP plays an important role in the control of platelet responsiveness to a variety of stimuli during acute inflammatory reactions.

Adenosine Triphosphate↗