TY - JOUR
T1 - GM‐CSF promotes proliferation of human fetal and adult microglia in primary cultures
AU - Lee, Sunhee C.
AU - Liu, Wei
AU - Brosnan, Celia F.
AU - Dickson, Dennis W.
N1 - Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.
PY - 1994/12
Y1 - 1994/12
N2 - Proliferation of microglia/macrophages is a common finding in many central nervous system diseases. To identify mitogenic signals for human microglia, we examined primary cultures of human fetal and adult microglia after stimulation with cytokines, colony stimulating factors (CSFs), or LPS, using proliferating cell nuclear antigen (PCNA) expression as an index of cell proliferation. The results showed that both M‐CSF and GM‐CSF induced microglial proliferation in fetal and adult human cultures, but that GM‐CSF provided a much stronger stimulus. At 96 h post‐stimulation, the mean PCNA labeling index was 2.4 for M‐CSF and 13.3 for GM‐CSF in fetal microglia; in adult microglia, the PCNA labeling index was 4.7 for M‐CSF and 9.0 for GM‐CSF. The effect of GM‐CSF on fetal microglia was dose dependent and synergistic with M‐CSF. LPS abolished the basal level of PCNA labeling in adult microglia, but in fetal microglia, caused a slight increase in PCNA labeling (1.9) at 96 h and consistently enhanced microglial cell survival and differentiation into highly branched cells. The production of GM‐CSF in purified human fetal astrocyte and microglial cultures was examined after stimulation with LPS, TNF‐α, or IL‐1β. Unlike M‐CSF, neither cell type produced GM‐CSF in unstimulated cultures; however, when stimulated with IL‐1β, astrocytes expressed GM‐CSF mRNA and protein, which accumulated in the culture through 72 h. In microglia, LPS was the only effective inducing agent. An immunocytochemical study performed to identify in vivo sources of GM‐CSF revealed selective labeling of reactive astrocytes in active lesions of multiple sclerosis and senile plaques of Alzheimer's disease. Our data demonstrate that both fetal and adult human microglia are capable of proliferation in response to CSFs, GM‐CSF being the more effective stimulus.
AB - Proliferation of microglia/macrophages is a common finding in many central nervous system diseases. To identify mitogenic signals for human microglia, we examined primary cultures of human fetal and adult microglia after stimulation with cytokines, colony stimulating factors (CSFs), or LPS, using proliferating cell nuclear antigen (PCNA) expression as an index of cell proliferation. The results showed that both M‐CSF and GM‐CSF induced microglial proliferation in fetal and adult human cultures, but that GM‐CSF provided a much stronger stimulus. At 96 h post‐stimulation, the mean PCNA labeling index was 2.4 for M‐CSF and 13.3 for GM‐CSF in fetal microglia; in adult microglia, the PCNA labeling index was 4.7 for M‐CSF and 9.0 for GM‐CSF. The effect of GM‐CSF on fetal microglia was dose dependent and synergistic with M‐CSF. LPS abolished the basal level of PCNA labeling in adult microglia, but in fetal microglia, caused a slight increase in PCNA labeling (1.9) at 96 h and consistently enhanced microglial cell survival and differentiation into highly branched cells. The production of GM‐CSF in purified human fetal astrocyte and microglial cultures was examined after stimulation with LPS, TNF‐α, or IL‐1β. Unlike M‐CSF, neither cell type produced GM‐CSF in unstimulated cultures; however, when stimulated with IL‐1β, astrocytes expressed GM‐CSF mRNA and protein, which accumulated in the culture through 72 h. In microglia, LPS was the only effective inducing agent. An immunocytochemical study performed to identify in vivo sources of GM‐CSF revealed selective labeling of reactive astrocytes in active lesions of multiple sclerosis and senile plaques of Alzheimer's disease. Our data demonstrate that both fetal and adult human microglia are capable of proliferation in response to CSFs, GM‐CSF being the more effective stimulus.
KW - Astrocytes
KW - Colony stimulating factor
KW - Culture
KW - Lipopolysaccharide
KW - Microglia
KW - Proliferating cell nuclear antigen
KW - human
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U2 - 10.1002/glia.440120407
DO - 10.1002/glia.440120407
M3 - Article
C2 - 7890333
AN - SCOPUS:0028675319
VL - 12
SP - 309
EP - 318
JO - GLIA
JF - GLIA
SN - 0894-1491
IS - 4
ER -