title: Differential regulation of macrophage phenotype by mature and pro-nerve growth factor.
abstract: To characterize the role of neurotrophin receptors on macrophages, we investigated the ability of nerve growth factor (NGF) and its precursor, proNGF, to regulate human macrophage phenotype. The p75 neurotrophin receptor (p75(NTR)) and TrkA were concentrated within overlapping domains on membrane ruffles. NGF stimulation of macrophages increased membrane ruffling, calcium spiking, phagocytosis and growth factor secretion. In contrast, proNGF induced podosome formation, increased migration, suppressed calcium spikes and increased neurotoxin secretion. These results demonstrate opposing roles of NGF and proNGF in macrophage regulation providing new avenues for pharmacological intervention during neuroinflammation.
authors.affiliation: Department of Neurology, University of North Carolina, Chapel Hill, NC 27599, United States; Neurobiology Curriculum, University of North Carolina, Chapel Hill, NC 27599, United States.
authors.forename: Kimberly S
authors.initials: KS
authors.lastname: Williams
authors.affiliation: Department of Neurology, University of North Carolina, Chapel Hill, NC 27599, United States.
authors.forename: Deirdre A
authors.initials: DA
authors.lastname: Killebrew
authors.affiliation: Department of Neurology, University of North Carolina, Chapel Hill, NC 27599, United States.
authors.forename: Gillian P
authors.initials: GP
authors.lastname: Clary
authors.affiliation: Department of Neurology, University of North Carolina, Chapel Hill, NC 27599, United States.
authors.forename: Jaimie A
authors.initials: JA
authors.lastname: Seawell
authors.affiliation: Department of Neurology, University of North Carolina, Chapel Hill, NC 27599, United States; Neurobiology Curriculum, University of North Carolina, Chapel Hill, NC 27599, United States. Electronic address: meekerr@neurology.unc.edu.
authors.forename: Rick B
authors.initials: RB
authors.lastname: Meeker
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000502:physiology; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D020932:Nerve Growth Factor / Q000494:pharmacology*; D010641:Phenotype; D011498:Protein Precursors / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans
chemical_list: D011498:Protein Precursors; C061397:pro-nerve growth factor, human; D020932:Nerve Growth Factor
keywords: Actin; Calcium; Inflammation; Monocyte; Neurodegeneration; Neurotrophin