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Microglial tissue plasminogen activator (tPA) triggers neuronal apoptosis in vitro
Author(s) -
Flavin M.P.,
Zhao G.,
Ho L.T.
Publication year - 2000
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/(sici)1098-1136(20000215)29:4<347::aid-glia5>3.0.co;2-8
Subject(s) - microglia , hippocampal formation , biology , apoptosis , lipopolysaccharide , programmed cell death , activator (genetics) , in vitro , microbiology and biotechnology , neuroscience , tissue plasminogen activator , immunology , inflammation , biochemistry , receptor
Several CNS disorders feature microglial activation. Microglia are known to have both restorative and cytotoxic capabilities. Neuronal apoptosis has been noted after an acute insult such as ischemia. Microglia may participate in this event. We previously showed that conditioned medium (CM) harvested from peritoneal macrophages or from activated microglia triggered apoptosis in rat hippocampal neurons in culture. We wished to characterize the factor responsible for triggering neuronal death. Quiescent microglia produced CM that did not disrupt hippocampal neurons. Lipopolysaccharide‐activated microglia produced CM which resulted in neuronal death. This effect was blocked by plasminogen activator inhibitor‐1, by tPA STOP, and by co‐incubation with tPA antibody. Recombinant human tPA exaggerated the neurotoxic effects of microglial CM, while tPA alone was toxic only at very high concentrations. This in vitro system, which probably excludes any significant impact of microglial free radicals, suggests that microglial tPA may contribute significantly to hippocampal neuronal death. GLIA 29:347–354, 2000. © 2000 Wiley‐Liss, Inc.