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

- Neurotrophin receptors p75NTR and TrkA are expressed on monocytes and macrophages.
- NGF and proNGF differentially regulate macrophage phenotypes; no evidence of M1/M2.
- NGF promotes membrane ruffling, calcium spiking and growth factor secretion.
- ProNGF induces podosome formation, migration and neurotoxin production.
- Novel therapeutic avenue for macrophage control during neuroinflammation

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 (p75NTR) 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.