title: Proteins from chromaffin granules promote survival of dorsal root ganglionic neurons: comparison with neurotrophins.
abstract: Neurotrophins are established survival and differentiation factors for sensory dorsal root ganglionic (DRG) neurons. We have previously shown that proteins from the secretory granules of adrenal chromaffin cells have a capacity to promote the survival of cultured chick DRG neurons. Using DRG neurons from embryonic day (E) 8 chick embryos we show now 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 neurotrophin, since the survival promoting effect can not be blocked by K252b, a specific inhibitor of the signal transduction pathways of neurotrophin high affinity receptors, (iv) partially blockable by antibodies to transforming growth factor-beta (TGF-beta) 1/2/3, and (v) more potent than any other out of 30 cytokines tested individually, including fibroblast growth factor (FGF)-5, epidermal growth factor (EGF), TGF-alpha, platelet-derived growth factor (PDGF)-AB, insulin-like growth 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 necrosis factor (TNF)-alpha, and interleukins (IL)-1 through -12. We conclude that chromaffin cells, which are known to receive a sensory innervation, can provide (a) trophic factor(s), which, in addition to neurotrophins, may be relevant for the maintenance of DRG neurons.
authors.affiliation: Department of Anatomy and Cell Biology III, University Heidelberg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Krieglstein
authors.forename: K
authors.initials: K
authors.lastname: Unsicker
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D002642:Chick Embryo; D019439:Chromaffin Cells / Q000737:chemistry / Q000648:ultrastructure; D002837:Chromaffin Granules / Q000737:chemistry* / Q000276:immunology; D016207:Cytokines / Q000494:pharmacology; D004357:Drug Synergism; D066246:ErbB Receptors / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology*; D008024:Ligands; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology; D020933:Neurotrophin 3; D009500:Neutralization Tests; D011506:Proteins / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000276:immunology*
chemical_list: D019138:Antibodies, Blocking; D016207:Cytokines; D008024:Ligands; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D020933:Neurotrophin 3; D011506:Proteins; D016212:Transforming Growth Factor beta; D066246:ErbB Receptors; C073922:neurotrophin 4