Exposure of cultured murine peritoneal macrophages to low concentrations of beryllium induces increases in intracellular calcium concentrations and stimulates DNA synthesis
Uk. Misra et al., Exposure of cultured murine peritoneal macrophages to low concentrations of beryllium induces increases in intracellular calcium concentrations and stimulates DNA synthesis, J LEUK BIOL, 65(6), 1999, pp. 786-791
Exposure of humans to beryllium dusts can induce a specific form of chronic
pnemnonitis that consists mainly of noncaseating granulomas in the lungs.
Multiple studies have documented both genetic and immune components of chro
nic berylliosis. Much work has focused on T cells and their reactivity in b
erylliosis, but less work has focused on the end effector cells in granulom
atous inflammation, macrophages. Because macrophages must become activated
to form granulomas, and they become activated by responding to numerous imm
unomodulatory signals, we investigated the effects of beryllium (BeCl2) on
a central signal transduction pathway in macrophages, increases in intracel
lular calcium ([Ca2+](i)). Exposure of cultured murine peritoneal macrophag
es to low, nontoxic concentrations induced successive spikes or oscillation
s in [Ca2+](i), Concentrations as low as 5 nM, induced significant increase
s in [Ca2+](i). The source of the increased [Ca2+](i) was exclusively extra
cellular in that increases in [Ca2+](i) could be completely blocked by chel
ating extracellular Ca2+, were inhibited by the Ca2+ channel blocker verapa
mil, and exposure of macrophages to BeCl2 had no effect on IP3 concentratio
ns. DNA synthesis, a Ca2+-sensitive function, was enhanced in dividing 1LN
cells and induced de novo in quiescent macrophages, Furthermore, BeCl2 enha
nced DNA synthesis iu the absence of coexposure to the protein kinase C act
ivator phorbol myristate acetate, These data support the hypothesis that be
ryllium toxicity is in part the result of altered Ca2+ metabolism in mononu
clear phagocytes consequent to reversible opening of plasma membrane channe
ls.