Skip to main content

Synergistic platelet activation by aggregates of IgG and the phospholipid platelet-activating factor 1-O-alkyl-2-acetyl-SN-glycero-3-phosphorylcholine

Journal of Clinical Immunology volume 6, pages 57–64 (1986)Cite this article

Abstract

Immune complexes and 1-O-alkyl-2-acetyl-SN-glycero-3-phosphorylcholine (AGEPC) are potent platelet-activating factors which interact with distinct receptors on human platelets. The mechanisms of platelet activation by these two stimuli were investigated by examining the effects of AGEPC on human platelets which had been preexposed to IgG aggregates (IgG-Agg). AGEPC and IgG-Agg in combination activated platelet aggregation synergistically, whereas release of the granular constituent serotonin was not increased. Synergy was maximal within 1 min of exposure of platelets to IgG-Agg and persisted for 5 to 10 min after exposure to IgG-Agg. Synergy was observed at concentrations of IgG-Agg which release platelet granular constituents with minimal aggregation. Monomeric IgG, which did not activate platelets, did not augment the platelet response to AGEPC. Platelet activation by AGEPC is enhanced by both the granular constituent adenosine diphosphate (ADP) and by arachidonic acid, suggesting that one or both agents may contribute to synergy between AGEPC and IgG-Agg. Indomethacin inhibited granule release by IgG-Agg and enhancement of AGEPC-induced platelet aggregation by IgG-Agg. The ADP scavengers creatine phosphate/creatine phosphokinase also blocked synergistic platelet activation. These data suggest that IgG-Agg releases platelet granule ADP by a cyclooxygenase-dependent mechanism and the released ADP, in combination with AGEPC, activates platelets synergistically.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

References

  1. Pinckard RN, McManus LM, Hanahan DJ: Chemistry and biology of acetyl glyceryl ether phosphorylcholine (platelet-activating factor).In Advances in Inflammation Research, Vol III, G Weissman (ed). New York, Raven Press, 1982, pp 147–180

    Google Scholar 

  2. Henson PM, Spiegelberg HL: Release of serotonin from human platelets induced by aggregated immunoglobulins of different classes and subclasses. J Clin Invest 52:1282–1288, 1973

    Google Scholar 

  3. Polley MJ, Nachman RL: Human platelet activation by C3a and C3a des-arg. J Exp Med 158:603–615, 1983

    Google Scholar 

  4. Charo IF, Feinman RD, Detwiler TC, Smith BJ, Ingerman CM, Silver MJ: Prostaglandin endoperoxides and thromboxane A2 can induce platelet aggregation in the absence of secretion. Nature 269:66–69, 1977

    Google Scholar 

  5. Pfueller SL, Weber S, Luscher EF: 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. J Immunol 118:514–524, 1977

    Google Scholar 

  6. Valone FH, Austen KF, Goetzl EJ: Identification of the platelet-activating activity in rheumatoid synovial fluid as an intermediate molecular weight complex of IgG. J Immunol 122:703–709, 1979

    Google Scholar 

  7. Valone FH, Coles E, Reinhold VR, Goetzl EJ: Specific binding of phospholipid platelet activating factor by human platelets. J Immunol 129:1637–1641, 1982

    Google Scholar 

  8. Valone FH: Isolation of a platelet membrane protein which binds the platelet-activating factor 1-0-hexadecyl-2-acetyl-SN-glycero-3-phosphorylcholine. Immunology 52:169–174, 1984

    Google Scholar 

  9. Betz SJ, Henson PM: Production and release of platelet-activating factor (PAF): Dissociation from degranulation and superoxide production in the human neutrophil. J Immunol 125:2756–2763, 1980

    Google Scholar 

  10. Camussi G, Aglietta M, Coda R, Bussolino F, Piacibello W, Tetta C: Release of platelet-activating factor (PAF) and histamine: Monocytes, polymorphonuclear neutrophils and basophils. Immunology 42:191–199, 1982

    Google Scholar 

  11. Camussi G, Bussolino F, Tetta C, Piacibello W, Aglietta M: Biosynthesis and release of platelet-activating factor from human monocytes. Int Arch Allerg Appl Immunol 70:245–253, 1983

    Google Scholar 

  12. Reinhold VN, Carr SA: Direct chemical ionization mass spectrometry with polyimide-coated wires. Anal Chem 54:499–511, 1982

    Google Scholar 

  13. Valone FH, Goetzl EJ: Specific binding by human polymorphonuclear leukocytes of the immunological mediator 1-0-hexadecyl/octadecyl-2-acetyl-sn-glycero-3-phosphorylcholine (AGEPC). Immunology 48:141–149, 1983

    Google Scholar 

  14. Marcus AJ, Safier LB, Ullman HL, Wong KTH, Broekman J, Weksler BB, Kaplan KL: Effects of acetyl glyceryl ether phosphorylcholine on human platelet function in vitro. Blood 58:1027–1032, 1981

    Google Scholar 

  15. Ostermann G, Till U, Thelmann K: Studies on the stimulation of human blood platelets by semi-synthetic plateletactivating factor. Thromb Res 30:127–136, 1983

    Google Scholar 

  16. Kinlough-Rathbone RL, Packham MA, Mustard JF: Synergism between platelet aggregating agents: The role of the arachidonate pathway. Thromb Res 11:567–575, 1977

    Google Scholar 

  17. Vargaftig BB, Fougue F, Benveniste J, Odiot J: Adrenaline and PAF-acether synergize to trigger cyclooxygenase-independent activation of plasma-free human platelets. Thromb Res 28:557–573, 1982

    Google Scholar 

  18. O'Flaherty JT, Lees CJ, Miller CH, McCall EE, Lewis JC, Love SH, Wykle RL: Selective densensitization of neutrophils: Further studies with 1-0-alkyl-SN-glycero-3-phosphocholine analogues. J Immunol 127:731–737, 1981

    Google Scholar 

  19. Yasaka T, Boxer LA, Baehner RL: Monocyte aggregation and superoxide anion release in response to formylmethionyl-leucyl-phenylalaine (FMLP) and platelet-activating factor (PAF). J Immunol 128:1939–1944, 1982

    Google Scholar 

Download references

Author information

Affiliations

  1. UCSF Hematology/Oncology Unit, VA Medical Center, 94121, San Francisco, California

    Frank H. Valone

Authors
  1. Frank H. Valone
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Valone, F.H. Synergistic platelet activation by aggregates of IgG and the phospholipid platelet-activating factor 1-O-alkyl-2-acetyl-SN-glycero-3-phosphorylcholine. J Clin Immunol 6, 57–64 (1986). https://doi.org/10.1007/BF00915365

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00915365

Key words

  • 1-O-Alkyl-2-acetyl-SN-glycero-3-phosphorylcholine
  • immune complexes
  • platelets
  • platelet-activating factor