Inhibition of microglia multinucleated giant cell formation and induction of differentiation by GM-CSF using a porcine in vitro model.
Multinucleated giant cell (MNGC) formation is an important histopathologic feature of AIDS dementia complex and tuberculous meningitis. We investigated the effect of several cytokines (GM-CSF, IFN-gamma, TNF-alpha, IL-3) and other stimuli (vaso-I, LPS, PMA) on MNGC formation in vitro by microglia from porcine neonatal brain. GM-CSF dose-dependently inhibited giant cell formation at physiological conditions (10 ng/ml) up till 4 days in culture. When confronted with a high concentration (1 microg/ml) they were 5.5 times less likely to form MNGC and 3.3 times more likely to develop a ramified morphology. In contrast, interferon-gamma (6 ng/ml) doubled the formation of MNGC. GM-CSF primed (4 days) microglia also produced significantly higher amounts of superoxide after PMA-stimulation. We conclude that GM-CSF leads microglia to a specific activation other than MNGC formation. Comparison of the present results with earlier reports on rodents reveals important inter-species differences.
Tambuyzer
Bart R
BR
Laboratory of Neurobiology and Neuropharmacology, Department of Biomedical Sciences, University of Antwerp, CDE, Universiteitsplein 1, B-2610 Wilrijk, Belgium.
Nouwen
Etienne J
EJ
D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000187:drug effects*; D018920:Coculture Techniques; D015726:Giant Cells / Q000166:cytology / Q000187:drug effects*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D007150:Immunohistochemistry; D017628:Microglia / Q000166:cytology / Q000187:drug effects*; D013481:Superoxides / Q000378:metabolism; D013552:Swine
D013481:Superoxides; D016178:Granulocyte-Macrophage Colony-Stimulating Factor