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J Neuroimmunol. 2015 Aug 15;285:76-93. doi: 10.1016/j.jneuroim.2015.05.016. Epub 2015 May 16.

Differential regulation of macrophage phenotype by mature and pro-nerve growth factor.

Author information

1
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.
2
Department of Neurology, University of North Carolina, Chapel Hill, NC 27599, United States.
3
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.

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.

KEYWORDS:

Actin; Calcium; Inflammation; Monocyte; Neurodegeneration; Neurotrophin

PMID:
26198923
PMCID:
PMC4528983
DOI:
10.1016/j.jneuroim.2015.05.016
[Indexed for MEDLINE]
Free PMC Article

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