Astrocytes modulate macrophage phagocytosis of myelin in vitro.
Previous work from this laboratory has shown that both macrophages and microglia phagocytize relatively little myelin in vitro under basal conditions. In an effort to better simulate the conditions within the central nervous system (CNS), we have co-cultured these cells with astrocytes, the most numerous of the neural cells in the CNS, and have compared myelin phagocytosis in the co-cultures with that in cells cultured alone. Both macrophages and microglia in company with astrocytes phagocytized about three times as much myelin as controls, as measured by the formation of cholesterol ester, while astrocytes alone showed little evidence of myelin phagocytosis. Astrocyte-conditioned medium increased phagocytic activity in macrophages by 2.3-fold, and by 3.5-fold in microglia. A number of adhesion molecules and extracellular matrices were tested for their effects on myelin phagocytosis. Matrigel was most effective in activating the macrophages, and in the presence of conditioned medium, stimulated these cells to phagocytize as much myelin as when co-cultured with astrocytes. On the other hand, Matrigel inhibited myelin phagocytosis in microglia. These results indicate that activation of macrophages by astrocytes may be due to an adhesion component, as well as to soluble factors secreted by the astrocytes. While microglia were also stimulated by conditioned medium, adhesion to astrocytes or Matrigel induced a downregulation in phagocytic activity.
Smith
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ME
Department of Neurology, Stanford University School of Medicine, CA 94305, USA. mesmith@leland.stanford.edu
Hoerner
M T
MT
D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000502:physiology; D003094:Collagen / Q000494:pharmacology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology; D004338:Drug Combinations; D016326:Extracellular Matrix Proteins / Q000502:physiology; D005260:Female; D007797:Laminin / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009186:Myelin Sheath / Q000502:physiology*; D010587:Phagocytosis / Q000187:drug effects / Q000502:physiology*; D011509:Proteoglycans / Q000494:pharmacology; D051381:Rats
D015815:Cell Adhesion Molecules; D017077:Culture Media, Conditioned; D016207:Cytokines; D004338:Drug Combinations; D016326:Extracellular Matrix Proteins; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen