Abstract
After differentiation either with exogenous macrophage (M) or with granulocyte/macrophage (GM) colony-stimulating factor (CSF) microglial cells were isolated from neonatal mouse brain cell cultures and were comparatively tested for secretory immune effector cell functions. Both factors obviously do not promote the development of cells with biased growth requirement; however, the two microglia populations displayed distinct potentials to produce inflammatory cytokines. Upon gradual stimulation by lipopolysaccharide, the cells harvested from M-CSF-driven culture released more interleukin-1 and tumor necrosis factor activity, GM-CSF-grown cells on the contrary proved superior in interleukin-6 secretion. This pattern was paralleled by correspondingly different kinetics of cytokine release in both types of microglial cells. When infected with Toxoplasma gondii only GM-CSF-differentiated cells were able to restrict the intracellular multiplication of tachyzoites in the absence of external stimuli. As described for interferon-γ-treated macrophages, the antiparasitic activity of this microglia population is due to the synthesis of reactive nitrogen intermediates, since it was antagonized by NG-monomethyl-L-arginine, a competitive inhibitor of the arginine-dependent metabolic pathway. Complementary to previous data which attest an intrinsic capability for antigen presentation to GM-CSF-grown microglia, the functional state of the cells elicited by M-CSF and GM-CSF, respectively, may correspond to the resting and an activated form of microglia as distinguished in vivo.
Original language | English (US) |
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Pages (from-to) | 193-201 |
Number of pages | 9 |
Journal | Journal of Neuroimmunology |
Volume | 45 |
Issue number | 1-2 |
DOIs | |
State | Published - Jun 1993 |
Bibliographical note
Funding Information:This work was supported by the Deutsche For-schungsgemeinschaft, SFB 194 project B8. We wish to thank our colleagues Drs. P. Hintz-Obertreis, L. Kaiser, M. Saathoff, F.R. Seiler, H.M. Seitz and J. Van Snick for their generous gifts of mAb, cell lines, cytokines or toxoplasms. We also thank K. Buchholz for testing indicator cell lines for mycoplasm contamination, G. Weichelt for typing and C. MacKenzie for critically reading the manuscript.
Keywords
- Colony-stimulating factors
- Cytokine secretion
- Microglia
- Nitric oxide
- Toxoplasma gondii