Activation of human monocytes and granulocytes by monoclonal antibodies to glycosylphosphatidelinositol‐anchored antigens

Fridtjof Lund‐Johansen, Johanna Olweus, Frank W. Symington, Aanen Arrli, John S. Thompson, Ramon Vilella, Keith Skubitz, Vaclav Horejsi

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The present study investigated possible receptor‐like characteristics of glycosyl‐phosphatidylinositol (GPI)‐linked antigens on human monocytes and granulocytes by measuring cytoplasmic calcium fluxes and the oxidative burst in cells following cross‐linking of GPI‐linked antigens. Cross‐linking of cell‐bound anti‐CD14, ‐CDw52 and ‐CD55 induced cytoplasmic calcium fluxes and oxidative bursts in unprimed human monocytes similar to those observed following FcyR cross‐linking. In granulocytes primed with 200 nM N‐formyl‐Met‐Leu‐Phe (FMLP), cross‐linking of cell‐bound anti‐CD16, ‐CD24, ‐CD59 and ‐CD67 led to calcium fluxes and activation of the oxidative burst. The oxidative bursts mediated by GPI‐linked antigens were stronger than those induced by 200 nM FMLP, even though FMLP induced a larger increase in cytoplasmic calcium concentration. The responses were likely to be independent of FcyR interactions as F(ab′)2 fragments of IgG or IgM antibodies were used in the experiments. Activating effects of monoclonal antibody to GPI‐linked antigens were not observed in cells from patients with paroxysmal nocturnal hemoglobinuria, which are deficient in GPI‐linked antigens. In addition, treatment with GPI‐specific phospholipase C led to inhibition of cell activation through GPI‐linked antigens but not through transmembrane receptors. Cross‐linking of a number of non‐GPI‐linked antigens (CD11a, CD18, CD31, CD35, CD43, and CD45) neither induced calcium fluxes, nor activated the oxidative burst. The results indicate that most, if not all, GPI‐linked surface glycoproteins on myeloid cells are capable of mediating cell activation and suggest that the GPI anchor is a structure facilitating signal transduction.

Original languageEnglish (US)
Pages (from-to)2782-2791
Number of pages10
JournalEuropean Journal of Immunology
Issue number11
StatePublished - Nov 1993


  • CD antigens
  • Calcium
  • Flow cytometry
  • NADPH oxidase
  • Signal transduction


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