Activation of human monocyte functions by tumor necrosis factor: rapid priming for enhanced release of superoxide and erythrophagocytosis, but no direct triggering of superoxide release

Exp Hematol. 1996 Mar;24(4):559-67.


Tumor necrosis factor (TNF), like granulocyte-macrophage colony-stimul ating factor (GM-CSF), rapidly primed human monocytes for enhanced release of superoxide (O-2) stimulated by receptor-mediated agonists, N-formyl-methionyl-leucyl-phenylalanine (FMLP) and concanavalin A (Con A), but not by phorbol myristate acetate (PMA), which bypasses the receptors to stimulate the cells. The optimal priming was obtained by pretreatment of suspended monocytes with 10 U/mL TNF for 10 minutes at 37 degrees C. The potency of the maximal priming effect was TNF> GM-CSF, and the combined effect of TNF and GM-CSF was greater than that of each cytokine alone. GM-CSF induced an increase in cytoplasmic pH but TNF did not. These findings suggest that TNF and GM-CSF activate monocytes through different mechanisms. TNF and GM-CSF by themselves never triggered O-2 release in suspended monocytes or monocytes adherent to endothelial cells, although both cytokines triggered massive release of O-2 in human neutrophils. In additions, TNF and GM-CSF induced tyrosine phosphorylation of a 42-kD protein in neutrophils but not in monocytes. These findings suggest that the TNF-receptor- or GM-CSF-receptor-mediated signaling pathways for triggering O-(2) release is active in neutrophils but inactive or defective in monocytes. TNF also enhanced phagocytosis of sialidase-treated autologous erythrocytes by monocytes, and this effect was further potentiated in the presence of autologous fresh serum. The significant enhancement of erythrophagocytosis was obtained at 1 U/mL TNF. At this concentration of TNF, the expression of C3bi-receptor (CD11b/CD18) was upregulated. These findings show that TNF rapidly primes human monocytes for enhanced release of O-(2) and erythrophagocytosis and suggest that TNF activates monocytes through autocrine or paracrine mechanisms at the inflammatory sites inasmuch as TNF is primarily produced by activated monocytes/macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Complement C3b / metabolism
  • Concanavalin A / pharmacology
  • Cytoplasm / physiology
  • Erythrocytes
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • Humans
  • Hydrogen-Ion Concentration
  • Monocytes / physiology*
  • N-Formylmethionine Leucyl-Phenylalanine / pharmacology
  • Phagocytosis
  • Phosphotyrosine / metabolism
  • Receptors, Leukocyte-Adhesion / metabolism
  • Recombinant Proteins
  • Superoxides / metabolism*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Time Factors
  • Tumor Necrosis Factor-alpha / physiology*


  • Receptors, Leukocyte-Adhesion
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Concanavalin A
  • Superoxides
  • Phosphotyrosine
  • N-Formylmethionine Leucyl-Phenylalanine
  • Complement C3b
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Tetradecanoylphorbol Acetate