FUNCTIONAL DICHOTOMY OF MOUSE MICROGLIA DEVELOPED IN-VITRO - DIFFERENTIAL-EFFECTS OF MACROPHAGE AND GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR ON CYTOKINE SECRETION AND ANTITOXOPLASMIC ACTIVITY

After differentiation either with exogenous macrophage (M) or with gra nulocyte/macrophage (GM) colony-stimulating factor (CSF) microglial ce lls were isolated from neonatal mouse brain cell cultures and were com paratively tested for secretory immune effector cell functions. Both f actors obviously do not promote the development of cells with biased g rowth requirement; however, the two microglia populations displayed di stinct potentials to produce inflammatory cytokines. Upon gradual stim ulation by lipopolysaccharide, the cells harvested from M-CSF-driven c ulture released more interleukin-1 and tumor necrosis factor activity, GM-CSF-grown cells on the contrary proved superior in interleukin-6 s ecretion. This pattern was paralleled by correspondingly different kin etics of cytokine release in both types of microglial cells. When infe cted with Toxoplasma gondii only GM-CSF-differentiated cells were able to restrict the intracellular multiplication of tachyzoites in the ab sence of external stimuli. As described for interferon-gamma-treated m acrophages, the antiparasitic activity of this microglia population is due to the synthesis of reactive nitrogen intermediates, since it was antagonized by N(G)-monomethyl-L-arginine, a competitive inhibitor of the arginine-dependent metabolic pathway. Complementary to previous d ata which attest an intrinsic capability for antigen presentation to G M-CSF-grown microglia, the functional state of the cells elicited by M -CSF and GM-CSF, respectively, may correspond to the resting and an ac tivated form of microglia as distinguished in vivo.