Production of hemopoietic colony-stimulating factors by astrocytes.
Astrocytes may play a central role in regulation of immune mediated processes in the central nervous system. By their inducible expression of MHC class II Ag and secretion of cytokines they may propagate expansion and activation of T and B lymphocytes invading the brain tissue. Here we report that astrocytes may also contribute to the macrophage response observed in inflammatory and degenerative diseases of the brain. Murine astrocytes secrete granulocyte-macrophage CSF (GM-CSF) as evidenced by induction of colony formation in bone marrow cells and growth of FDC-P1 cells. Both effects are neutralized with anti-GM-CSF- but not with anti-IL-3-antibodies. Some residual activity detected in the bone marrow assay after antibody treatment can be explained by concomitant production of granulocyte CSF (G-CSF). The mRNA of both G- and GM-CSF are identified by Northern blots in astrocytes. Furthermore, mRNA for IL-1 alpha and IL-1 beta are detected in comparable amounts in astrocytes and brain macrophages, the latter, however, comprising much more potent sources of TNF-alpha.
Malipiero
U V
UV
Section of Clinical Immunology, University Hospital, Zürich, Switzerland.
Frei
K
K
Fontana
A
A
D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D015152:Blotting, Northern; D003115:Colony-Stimulating Factors / Q000096:biosynthesis* / Q000235:genetics; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000096:biosynthesis* / Q000235:genetics; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D007377:Interleukin-3 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation; D051379:Mice; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007375:Interleukin-1; D007377:Interleukin-3; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor