title: Nerve growth factor and cytokines mediate lymphoid tissue-induced neurite outgrowth from mouse superior cervical ganglia in vitro.
abstract: Superior cervical ganglia (SCG) from neonatal mice were cultured with adult murine lymphoid tissue explants in Matrigel (Collaborative Biomedical, Bedford, MA). After 1 and 2 days in culture, many neurites grew toward thymus and spleen. Normal mesenteric lymph node (MLN) induced a smaller effect; however, activated MLN (isolated from mice 10 days after infection with Nippostrongylus brasiliensis; Nb-MLN-10d) caused significantly increased neurite outgrowth. To determine the roles of nerve growth factor (NGF) and cytokines in the promotion of neuritogenesis by lymphoid tissues, anti-NGF and various anti-cytokines were added to cocultures. Anti-NGF inhibited most of the neurite outgrowth toward thymus and spleen but only partially that toward Nb-MLN-10d. Anti-mouse IL-1 beta also significantly reduced the number of neurites growing toward thymus, spleen, and normal MLN. The number of neurites growing toward Nb-MLN-10d was significantly reduced by anti-IL-1 beta, anti-IL-3, anti-IL-6, or anti-GM-CSF. Exogenous IL-1 beta and IL-3 caused neurite outgrowth in single SCG cultures; and the IL-1 beta-, but not the IL-3-, mediated effect was completely blocked by anti-NGF. In one-day thymus/SCG cocultures, endogenous IL-1 was not detectable at concentrations sufficient to cause nerve growth; however, ample NGF was present in the thymic tissues and culture supernatants, but not in SCG. These data suggest that IL-1 mediates NGF production in lymphoid tissues, which in turn induces the growth of sympathetic nerves. Moreover, IL-3, IL-6, or GM-CSF produced during inflammation might also play important roles in the stimulation of nerve growth in vivo.
authors.affiliation: Intestinal Disease Research Programme, Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Y
authors.initials: Y
authors.lastname: Kannan
authors.forename: J
authors.initials: J
authors.lastname: Bienenstock
authors.forename: M
authors.initials: M
authors.lastname: Ohta
authors.forename: A M
authors.initials: AM
authors.lastname: Stanisz
authors.forename: R H
authors.initials: RH
authors.lastname: Stead
mesh_terms: D000818:Animals; D046508:Culture Techniques; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology*; D005260:Female; D007106:Immune Sera / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D008198:Lymph Nodes / Q000469:parasitology / Q000502:physiology; D008221:Lymphoid Tissue / Q000469:parasitology / Q000502:physiology*; D008297:Male; D008643:Mesentery; D051379:Mice; D008815:Mice, Inbred Strains; D009414:Nerve Growth Factors / Q000276:immunology / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D011247:Pregnancy; D017206:Strongylida Infections / Q000276:immunology / Q000503:physiopathology; D017783:Superior Cervical Ganglion / Q000187:drug effects* / Q000254:growth & development*
chemical_list: D016207:Cytokines; D007106:Immune Sera; D007375:Interleukin-1; D007377:Interleukin-3; D009414:Nerve Growth Factors