MODULATION OF FC-GAMMA RECEPTOR-MEDIATED EARLY EVENTS BY THE TYROSINEPHOSPHATASE CD45 IN PRIMARY HUMAN MONOCYTES - CONSEQUENCES FOR INTERLEUKIN-6 PRODUCTION

Stimulation of primary human monocytes from several donors by cross-li nking of Fc gamma receptor type I (Fc gamma RI) and Fc gamma RII gave rise to calcium mobilization and protein tyrosine phosphorylation. The se early events were not observed without cross-linking. CD45, a trans membrane tyrosine phosphatase, when co-crosslinked with either Fc gamm a RI or Fc gamma RII, could prevent Fc gamma RI and Fc gamma RII-media ted calcium mobilization and protein tyrosine phosphorylation. When in terleukin (IL)-6 production was measured, we noted a strong IL-6 produ ction after activation of primary human monocytes by cross-linking of Fc gamma RI or Fc gamma RII. In contrast to calcium mobilization and t yrosine phosphorylation of proteins, IL-6 production was not affected by co-cross-linking of CD45 with either Fc gamma RI or Fc gamma RII. I nterestingly, cross-linking of the CD45 itself was sufficient to induc e IL-6 production. Our results show that the CD45 molecule is importan t in modulating early events following stimulation of primary human mo nocytes by cross-linking of Fc gamma RI or Fc gamma RII. However, trig gering of CD45 alone can also induce IL-6 production, indicating that CD45 ligation itself can give signals and may have an important role i n cytokine induction pathways.