FUNCTIONAL-PROPERTIES OF MURINE MACROPHAGES PROMOTED BY NERVE GROWTH-FACTOR

The stimulating effect of nerve growth factor (NGF) on phagocytosis, p arasite killing, and interleukin-1 beta (IL-1 beta) production of muri ne peritoneal macrophages was assessed. In the presence of various dos es of NGF, macrophages showed the increased phagocytosis of both nonsp ecific hydrophilic microspheres and sheep red blood cells (SRBC) opson ized 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 optima l dose of recombinant granulocyte-macrophage colony-stimulating factor or recombinant interferon-gamma. The addition of NGF to peritoneal ma crophages and monocyte-macrophage J774A.1 cells led to a significant r elease of IL-1 beta in a dose-dependent manner and expression of IL-1 beta 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 p140(trk) phosphorylation a nd because flow cytometric analysis with specific Ab against two disti nct NGF receptors showed the expression of p140(trk) unlike p75(LNGFR) . On the surface of macrophages, the stimulating activity of NGF to mu rine macrophages may be mediated through p140(trk). Thus, NGF may act as an activator for murine macrophages in the process of inflammatory and immune actions. (C) 1996 by The American Society of Hematology.