Substance P, the most abundant neurokinin in the CNS, is a major modulator
of the immune system. We have examined the gene expression of substance P a
nd its receptor in human fetal brain microglia. Using reverse transcription
-polymerase chain reaction and Southern blotting assay, the four isoforms o
f preprotachykinin-A gene transcripts (alpha, beta, gamma and delta) were d
etected in the microglia. The human fetal microglia produced significantly
higher levels of endogenous substance P protein (640-850 pg/10(6) cells) th
an did human peripheral blood monocyte-derived macrophages (25-50pg/10(6) c
ells), as determined by an enzyme immunoassay. Using immunohistochemical st
aining with an anti-substance P antibody, cell membrane substance P immunor
eactivity was observed. In addition, we identified the presence of messenge
r RNA for neurokinin-1 receptor, a primary receptor for substance P in huma
n fetal microglia.
From these data, we propose that substance P and its receptor are biologica
lly involved in regulating the functions of microglia, and potentially play
an important role in host defense of the central nervous system. (C) 2000
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