RANTES promotes growth and survival of human first-trimester forebrain astrocytes

We have examined the role of alpha and beta chemokines in the promotion of the ontogenetic development of the brain. RANTES was expressed preferential ly in human fetal astrocytes in an age-dependent manner. Astrocytes from 5- week-old brains showed high proliferation and reduced survival, whereas 10- week-old astrocytes exhibited opposite effects. These effects were suppress ed by anti-RANTES or anti-RANTES receptor antibodies and were enhanced by r ecombinant RANTES. RANTES induced tyrosine phosphorylation of several cellu lar proteins and nuclear translocation of STAT-1 in astrocytes. Interferons (IFN-gamma) was required for RANTES effects because RANTES induced IFN-gam ma, and only 10-week-old astrocytes expressed the IFN-gamma receptor. Block ing of IFN-gamma with antibody reversed the effects of RANTES, indicating t hat cytokine/chemokine networks are critically involved in brain developmen t.