Modulation of Fc gamma receptor-mediated early events by the tyrosine phosphatase CD45 in primary human monocytes. Consequences for interleukin-6 production.
Stimulation of primary human monocytes from several donors by cross-linking of Fc gamma receptor type I (Fc gamma RI) and Fc gamma RII gave rise to calcium mobilization and protein tyrosine phosphorylation. These early events were not observed without cross-linking. CD45, a transmembrane tyrosine phosphatase, when co-cross-linked with either Fc gamma RI or Fc gamma RII, could prevent Fc gamma RI and Fc gamma RII-mediated calcium mobilization and protein tyrosine phosphorylation. When interleukin (IL)-6 production was measured, we noted a strong IL-6 production after activation of primary human monocytes by cross-linking of Fc gamma RI or Fc gamma RII. In contrast to calcium mobilization and tyrosine phosphorylation of proteins, IL-6 production was not affected by co-cross-linking of CD45 with either Fc gamma RI or Fc gamma RII. Interestingly, cross-linking of the CD45 itself was sufficient to induce IL-6 production. Our results show that the CD45 molecule is important in modulating early events following stimulation of primary human monocytes by cross-linking of Fc gamma RI or Fc gamma RII. However, triggering of CD45 alone can also induce IL-6 production, indicating that CD45 ligation itself can give signals and may have an important role in cytokine induction pathways.
Corvaïa
N
N
Sandoz Research Institute, Department of Immune Regulation (Cellular Biology I), Vienna, Austria.
Reischl
I G
IG
Kroemer
E
E
Mudde
G C
GC
D000911:Antibodies, Monoclonal / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis*; D017493:Leukocyte Common Antigens / Q000276:immunology / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology*; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism / Q000502:physiology*; D014638:Vanadates / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D015850:Interleukin-6; D017452:Receptors, IgG; D014638:Vanadates; D011505:Protein-Tyrosine Kinases; D017493:Leukocyte Common Antigens; D017027:Protein Tyrosine Phosphatases; D002118:Calcium