PROTEINS FROM CHROMAFFIN GRANULES PROMOTE SURVIVAL OF DORSAL-ROOT GANGLIONIC NEURONS - COMPARISON WITH NEUROTROPHINS

Neurotrophins are established survival and differentiation factors for sensory dorsal root ganglionic (DRG) neurons. We have previously show n that proteins from the secretory granules of adrenal chromaffin cell s have a capacity to promote the survival of cultured chick DRG neuron s. Using DRG neurons from embryonic day (E) 8 chick embryos we show no w that this material is (i) as effective as nerve growth factor (NGF), (ii) additive to NGF, neurotrophin-3, or -4, (iii) unlikely to be a n eurotrophin, since the survival promoting effect can not be blocked by K252b, a specific inhibitor of the signal transduction pathways of ne urotrophin high affinity receptors, (iv) partially blockable by antibo dies to transforming growth factor-beta (TGF-beta) 1/2/3, and (v) more potent than any other out of 30 cytokines tested individually, includ ing fibroblast growth factor (FGF)-5, epidermal growth factor (EGF), T GF-alpha, platelet-derived growth factor (PDGF)-AB, insulin-like growt h factors (IGF)-I and -II, leukemia inhibitory factor (LIF), TGF-beta, glial cell line-derived neurotrophic factor (GDNF), stem cell factor, granulocyte-colony stimulating factor (G-CSF), oncostatin M, tumor ne crosis factor (TNF)-alpha, and interleukins (IL)-1 through -12. We con clude that chromaffin cells, which art: known to receive a sensory inn ervation, can provide (a) trophic factor(s), which, in addition to neu rotrophins, may be relevant for the maintenance of DRG neurons.