Morphological transformation of microglia in vitro

doi:10.1016/0006-8993(91)91302-H

Brain Research

Volume 545, Issues 1–2, 5 April 1991, Pages 301-306

https://doi.org/10.1016/0006-8993(91)91302-H Get rights and content

Abstract

Isolated microglia underwent in vitro morphological transformation to amboid, rod-shaped and ramified forms in response to several cytokines, factors from astrocytes, or factors which affect macrophage function. These morphological transformations were reversible. Examination of the enzymatic activity, superoxide anion formation and proliferative activity of these transformed microglia indicated that the ameboid forms were activated, rod-shaped microglia were proliferating, and the ramified forms were resting microglia.

Reference (17)

LingE.A.
The origin and nature of microglia
OhnoK. et al.
Production of granulocyte/macrophage colony-stimulating factor by cultured astrocytes
Biochem. Biophys. Res. Commun.
(1990)
SawadaM. et al.
Production of tumor necrosis factor-alpha by microglia and astrocytes in culture
Brain Research
(1989)
SawadaM. et al.
Activation and proliferation of isolated microglia by colony stimulating factor-1 and possible involvement of protein kinase C
Brain Research
(1990)
SuzumuraA. et al.
MHC antigen expression on bulk isolated macrophage-microglia from newborn mouse brain: induction of Ia antigen expression by γ-interferon
J. Neuroimmunol.
(1987)
SuzumuraA. et al.
Effects of colony-stimulating factors on isolated microglia in vitro
J. Neuroimmunol.
(1990)
BaileyF.W.
Trauma of the spinal cord
ChungI.Y. et al.
Tumor necrosis factor-α production by astrocytes: induction by lipopolysaccharide, IFN-γ and IL-1 β
J. Immunol.
(1990)

There are more references available in the full text version of this article.

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Morphological transformation of microglia in vitro

Abstract

Biochem. Biophys. Res. Commun.

Brain Research

Brain Research

J. Neuroimmunol.

J. Neuroimmunol.

Trauma of the spinal cord

Tumor necrosis factor-α production by astrocytes: induction by lipopolysaccharide, IFN-γ and IL-1 β

J. Immunol.