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Functional properties of murine macrophages promoted by nerve growth factor
Y Susaki1, S Shimizu, K Katakura
1Department of Veterinary Clinic, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Japan.
Abstract:
The stimulating effect of nerve growth factor (NGF) on phagocytosis, parasite killing, and interleukin-1beta (IL-1beta) production of murine peritoneal macrophages was assessed. In the presence of various doses of NGF, macrophages showed the increased phagocytosis of both nonspecific hydrophilic microspheres and sheep red blood cells (SRBC) opsonized with anti-SRBC antibodies (Ab) or complement in a dose-dependent manner. NGF also enhanced killing of Leishmania donovani promastigotes by macrophages, and its ability was comparable with that of an optimal dose of recombinant granulocyte-macrophage colony-stimulating factor or recombinant interferon-gamma. The addition of NGF to peritoneal macrophages and monocyte-macrophage J774A.1 cells led to a significant release of IL-1beta in a dose-dependent manner and expression of IL-1beta mRNA. Because pretreatment of peritoneal macrophages and J774A.1 cells with K-252a, a tyrosine kinase inhibitor, completely suppressed these NGF-mediated stimulating effects and p140trk phosphorylation and because flow cytometric analysis with specific Ab against two distinct NGF receptors showed the expression of p140trk, unlike p75LNGFR, on the surface of macrophages, the stimulating activity of NGF to murine macrophages may be mediated through p140trk. Thus, NGF may act as an activator for murine macrophages in the process of inflammatory and immune actions.
Insights
Nerve growth factor (NGF) activates murine macrophages, enhancing their ability to engulf pathogens and produce interleukin-1beta (IL-1beta). This immune-boosting effect is mediated through the p140trk receptor, highlighting NGF
Area of Science:
- Immunology
- Cell Biology
- Neuroscience
Background:
- Nerve growth factor (NGF) is crucial for neuronal development and survival.
- The role of NGF in innate immune responses, particularly macrophage activation, is less understood.
- Macrophages play a key role in host defense against pathogens and in inflammatory processes.
Purpose of the Study:
- To investigate the effects of NGF on murine peritoneal macrophage functions.
- To determine if NGF influences phagocytosis, parasite killing, and cytokine production.
- To elucidate the signaling pathway involved in NGF-mediated macrophage activation.
Main Methods:
- Murine peritoneal macrophages and J774A.1 cell line were treated with varying doses of NGF.
- Phagocytosis assays were performed using microspheres and antibody/complement-opsonized sheep red blood cells (SRBC).
- Parasite killing assays involved Leishmania donovani promastigotes.
- Interleukin-1beta (IL-1beta) production and mRNA expression were measured.
- Tyrosine kinase inhibitor K-252a and flow cytometry were used to investigate signaling pathways and receptor expression (p140trk and p75LNGFR).
Main Results:
- NGF significantly enhanced macrophage phagocytosis of both nonspecific microspheres and opsonized SRBC in a dose-dependent manner.
- NGF promoted the killing of Leishmania donovani promastigotes, with efficacy comparable to recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon-gamma (IFN-γ).
- NGF stimulated the release of IL-1beta and increased IL-1beta mRNA expression in macrophages.
- Pretreatment with K-252a abolished NGF-induced effects, indicating the involvement of tyrosine kinase signaling.
- Flow cytometry confirmed the expression of the p140trk receptor, but not p75LNGFR, on macrophages, suggesting p140trk mediates NGF's action.
Conclusions:
- NGF acts as a potent activator of murine macrophages.
- NGF enhances key macrophage functions including phagocytosis, parasite clearance, and pro-inflammatory cytokine production.
- The observed effects of NGF on macrophages are primarily mediated through the p140trk receptor tyrosine kinase pathway.
- NGF may play a significant role in modulating inflammatory and immune responses.