, Volume 16, Issue 1, pp 31–44 | Cite as

Inhibition of release of arachidonic acid, superoxide, and IL-1 from human monocytes by monoclonal anti-HLA class II antibodies: Effects at proximal and distal points of inositol phospholipid hydrolysis pathway

  • Joseph Puri
  • Michael Taplits
  • Maria Alava
  • Ezio Bonvini
  • Thomas Hoffman
Original Articles


Incubation of human elutriator-purified monocytes with anti-HLA-DR or DQ antibody inhibited the release of arachidonic acid induced by serum-treated zymosan (STZ), a phagocytic stimulus that is known to induce inositol phospholipid hydrolysis and Ca2+ influx. However, only anti-HLA-DR antibody partially inhibited STZ-induced inositol phospholipid hydrolysis and concanavalin-A-induced Ca2+ influx. Incubation with anti-HLA-DR or -DQ antibody inhibited phorbol ester-induced AA release as well as superoxide production and IL-1 release. Inhibition of monocyte function by anti-class II antibodies was not accompanied by cAMP elevation. Furthermore, addition of exogenous db-cAMP and other agents (forskolin, cholera toxin, or 3-isobutyl-1-methyl-xanthine) that increase cAMP levels through different mechanisms, a one or in combination with anti-HLA antibodies, had no inhibitory effect on factor release. Our results demonstrate that perturbation of class II molecules down-modulates cell activation at more than one point of the signal transduction pathway with dominant inhibition distal to inositol phospholipid hydrolysis. They also suggest that the inhibition by anti-HLA class II antibody is probably not mediated via cAMP elevation.


Arachidonic Acid Cholera Phorbol Forskolin Cholera Toxin 
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Copyright information

© Plenum Publishing Corporation 1992

Authors and Affiliations

  • Joseph Puri
    • 2
    • 1
  • Michael Taplits
    • 2
  • Maria Alava
    • 2
  • Ezio Bonvini
    • 2
  • Thomas Hoffman
    • 2
  1. 1.Laboratory of Cell Biology, Division of HematologyCenter for Biologies Evaluation and Research U.S. Food and Drug AdministrationBethesda
  2. 2.The Weizmann Institute of ScienceRehovotIsrael

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