DIFFERENTIAL INDUCTION OF APOPTOSIS BY FAS-FAS LIGAND INTERACTIONS INHUMAN MONOCYTES AND MACROPHAGES

Human monocytes undergo spontaneous apoptosis upon culture in vitro; r emoval of serum from the media dramatically increases the rate of this process. Monocyte apoptosis can be significantly abrogated by the add ition of growth factors or proinflammatory mediators. We have evaluate d the role of the endogenous Fas-Fas Ligand (FasL) interaction in the induction of this spontaneous apoptosis and found that a Fas-immunoglo bulin (Ig) fusion protein, an antagonistic anti-Fas monoclonal antibod y and a rabbit anti-FasL antibody all greatly reduced the onset of apo ptosis. The results indicate that spontaneous death of monocytes is me diated via an autocrine or paracrine pathway. Treatment of the cells w ith growth factors or cytokines that prevented spontaneous apoptosis h ad no major effects on the expression of Fas or FasL. Additionally, mo nocyte-derived macrophages were found to express both Fas and FasL but did not undergo spontaneous apoptosis and were not sensitive to stimu lation by an agonistic anti-Fas IgM. These results indicate that prote ctive mechanisms in these cells exist at a site downstream of the rece ptor-ligand interaction.