title: Neutrophils express oncomodulin and promote optic nerve regeneration.
abstract: Although neurons are normally unable to regenerate their axons after injury to the CNS, this situation can be partially reversed by activating the innate immune system. In a widely studied instance of this phenomenon, proinflammatory agents have been shown to cause retinal ganglion cells, the projection neurons of the eye, to regenerate lengthy axons through the injured optic nerve. However, the role of different molecules and cell populations in mediating this phenomenon remains unclear. We show here that neutrophils, the first responders of the innate immune system, play a central role in inflammation-induced regeneration. Numerous neutrophils enter the mouse eye within a few hours of inducing an inflammatory reaction and express high levels of the atypical growth factor oncomodulin (Ocm). Immunodepletion of neutrophils diminished Ocm levels in the eye without altering levels of CNTF, leukemia inhibitory factor, or IL-6, and suppressed the proregenerative effects of inflammation. A peptide antagonist of Ocm suppressed regeneration as effectively as neutrophil depletion. Macrophages enter the eye later in the inflammatory process but appear to be insufficient to stimulate extensive regeneration in the absence of neutrophils. These data provide the first evidence that neutrophils are a major source of Ocm and can promote axon regeneration in the CNS.
authors.affiliation: Laboratories for Neuroscience Research in Neurosurgery and F.M. Kirby Neurobiology Center, Children's Hospital, Boston, Massachussetts 02115, Department of Ophthalmology, Osaka Medical College, Osaka 569-8686, Japan, and Departments of Surgery and Ophthalmology and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Takuji
authors.initials: T
authors.lastname: Kurimoto
authors.forename: Yuqin
authors.initials: Y
authors.lastname: Yin
authors.forename: Ghaith
authors.initials: G
authors.lastname: Habboub
authors.forename: Hui-Ya
authors.initials: HY
authors.lastname: Gilbert
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Li
authors.forename: Shintaro
authors.initials: S
authors.lastname: Nakao
authors.forename: Ali
authors.initials: A
authors.lastname: Hafezi-Moghadam
authors.forename: Larry I
authors.initials: LI
authors.lastname: Benowitz
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D020934:Ciliary Neurotrophic Factor / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D053605:Leukemia Inhibitory Factor / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000502:physiology*; D009504:Neutrophils / Q000378:metabolism*; D009901:Optic Nerve Diseases / Q000473:pathology* / Q000503:physiopathology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D012160:Retina / Q000166:cytology; D012165:Retinal Ganglion Cells / Q000378:metabolism; D013266:Stilbamidines / Q000378:metabolism; D014795:Visual Pathways / Q000502:physiology
chemical_list: C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D015703:Antigens, CD; D002135:Calcium-Binding Proteins; D020934:Ciliary Neurotrophic Factor; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D011956:Receptors, Cell Surface; D013266:Stilbamidines; C551746:granulocyte receptor 1, mouse; C034733:oncomodulin
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