Leukemia inhibitory factor determines the growth status of injured adult sensory neurons.
Conditioning injury to adult mammalian sensory neurons enhances their regeneration potential. Here we show that leukemia inhibitory factor (LIF) is a fundamental component of the conditioning response. Conditioning injury in vivo significantly increases the intrinsic growth capacity of sensory neurons in vitro from LIF+/+ mice. This conditioning effect is significantly blunted in sensory neurons from LIF-/- mice. Enhanced growth is rescued in vitro in LIF-/- mice by the addition of exogenous LIF, and the effect blocked by human LIF-05, an LIF receptor antagonist. Furthermore, we demonstrate that LIF promotes elongating but not arborizing neurite outgrowth in vitro and is required for normal regeneration of injured adult sensory neurons in vivo. LIF is also functionally protective to peptidergic sensory neurons after nerve damage in vivo. Our results indicate that the alteration in intrinsic growth status of injured sensory neurons depends, at least in part, on LIF.
Cafferty
W B
WB
Centre for Neuroscience Research, Guy's, King's, and St. Thomas' School of Biomedical Science, King's College London, London SE1 1UL, United Kingdom.
Gardiner
N J
NJ
Gavazzi
I
I
Powell
J
J
McMahon
S B
SB
Heath
J K
JK
Munson
J
J
Cohen
J
J
Thompson
S W
SW
D000818:Animals; D019771:Axotomy; D015740:Calcitonin Gene-Related Peptide / Q000096:biosynthesis; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019610:Cytoprotection / Q000187:drug effects; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects; D006131:Growth Inhibitors / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D007278:Injections, Spinal; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009412:Nerve Fibers / Q000378:metabolism; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010641:Phenotype; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000502:physiology; D013979:Tibial Nerve / Q000502:physiology
D006131:Growth Inhibitors; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D015740:Calcitonin Gene-Related Peptide