Induction of functional interleukin-2 receptor in mouse microglia.
Interleukin (IL)-2, initially discovered for its mitogenic activity on T cells, also acts on monocytes, resulting in the activation of cytokine production, superoxide production, and tumoricidal activity. Because severe brain damage was observed in IL-2-transgenic mice, this cytokine may have some influence(s) on the cells of the CNS. We investigated IL-2 receptor-bearing cells in the CNS and found that activated microglia expressed alpha-chain mRNA and immunoreactive IL-2 receptor beta-chain protein in culture. Although microglia did not express IL-2 receptors under normal culture conditions, they were induced to express these receptors by lipopolysaccharide (LPS) in a time-dependent manner. The IL-2 receptors were found to be functional because the viability and growth activity of LPS-treated microglia, but not untreated controls, increased in response to recombinant mouse IL-2 as determined by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay and bromodeoxyuridine uptake experiment, respectively. These effects of recombinant IL-2 were blocked by pretreatment with anti-mouse IL-2 receptor beta-chain antibody. Our findings suggest that activated microglia in the CNS can respond to this T cell-derived factor regulating their growth, which may be an important mechanism of communication between nervous and immune systems in physiological and pathological conditions.
Sawada
M
M
Division of Cell Biology, Institute for Comprehensive Medical Science, School of Medicine, Fujita Health University, Aichi, Japan.
Suzumura
A
A
Marunouchi
T
T
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001483:Base Sequence; D001973:Bromodeoxyuridine / Q000378:metabolism; D002478:Cells, Cultured; D015870:Gene Expression; D007376:Interleukin-2 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000378:metabolism*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism
D000906:Antibodies; D007376:Interleukin-2; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D013778:Tetrazolium Salts; D013844:Thiazoles; D012194:RNA-Directed DNA Polymerase; C022616:thiazolyl blue; D001973:Bromodeoxyuridine