Functional properties of murine macrophages promoted by nerve growth factor.
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.
Susaki
Y
Y
Department of Veterinary Clinic, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Japan.
Shimizu
S
S
Katakura
K
K
Watanabe
N
N
Kawamoto
K
K
Matsumoto
M
M
Tsudzuki
M
M
Furusaka
T
T
Kitamura
Y
Y
Matsuda
H
H
D016475:3T3 Cells / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002227:Carbazoles / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D026121:Indole Alkaloids; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics; D007893:Leishmania donovani / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000469:parasitology / Q000502:physiology*; D008297:Male; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology*; D016716:PC12 Cells / Q000737:chemistry / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis / Q000378:metabolism
D002227:Carbazoles; D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; D007375:Interleukin-1; D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor; C049985:staurosporine aglycone; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA