Exposure of cultured murine peritoneal macrophages to low concentrations of beryllium induces increases in intracellular calcium concentrations and stimulates DNA synthesis

Citation
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
Citations number
19
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Immunology
Journal title
JOURNAL OF LEUKOCYTE BIOLOGY
ISSN journal
0741-5400 → ACNP
Volume
65
Issue
6
Year of publication
1999
Pages
786 - 791
Database
ISI
SICI code
0741-5400(199906)65:6<786:EOCMPM>2.0.ZU;2-M
Abstract
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.