K. Williams et al., ACTIVATION OF ADULT HUMAN-DERIVED MICROGLIA BY MYELIN PHAGOCYTOSIS IN-VITRO, Journal of neuroscience research, 38(4), 1994, pp. 433-443
The present study was designed to determine the extent to which cultur
ed glial cells phagocytose normal central nervous system (CNS) myelin
and CNS myelin opsonized with serum or purified antibody against myeli
n basic protein (MBP). Glial cells studied were mixed cultures (consis
ting of astrocyte, microglia, and oligodendrocytes) and enriched micro
glia established from adult human brain specimens and enriched astrocy
tes from fetal human brain. A human monocytic cell line, THP-1, was in
cluded as a control. Uptake of I-125-labelled myelin was followed over
a 24 hr time period. An assay of oxidative burst (30 min) and cytokin
e bioassays measuring IL-1, IL-6, and tumor necrosis factor (TNF) prod
uction (6-48 hr) were used to investigate short- and long-term activat
ion of phagocytosing cells. Maximum myelin uptake by phagocytosing gli
al cells occurred within 12-24 hr following myelin incubation. Opsoniz
ation of myelin prior to the phagocytosis assay resulted in greater my
elin uptake by mixed glial cell cultures, microglia, and THP-1 cells o
ver that of nontreated myelin. The magnitude of myelin phagocytosis by
astrocytes was considerably lower than microglia and THP-1, and was n
ot affected by myelin opsonization. Within 30 min of myelin phagocytos
is, microglia and THP-1 cells underwent oxidative burst; opsonization
of myelin by purified anti-MBP IgG and heat-inactivated serum enhanced
the microglial oxidative burst activity. Production of IL-1, TNF, and
most markedly IL-6 by microglia was increased following 12-24 hr of m
yelin ingestion. Our data demonstrate that myelin phagocytosis by adul
t human-derived microglia occurs in vitro, is augmented when myelin is
opsonized, and results in the activation of microglia as assessed by
oxidative burst and cytokine production. (C) 1994 Wiley-Liss, Inc.