Role of calcium in the induction of TNFα expression by macrophages on exposure to ultrafine particles

D. M. Brown, K. Donaldson, V. Stone

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Ultrafine particles have been suggested to be one of the components responsible for the adverse health effects of environmental particulate air pollution (PM 10). This study aimed to investigate the ability of fine and ultrafine carbon black (ufCB) particles to stimulate production of the pro-inflammatory cytokine tumour necrosis factor alpha (TNFα) by primary rat alveolar macrophages. We have previously demonstrated that ufCB, but not fine CB, is able to enhance calcium influx into macrophages in the presence of a secondary calcium agonist such as thapsigargin. For this reason, we also investigated the role of intracellular calcium signalling in controlling ufCB-induced TNFα production. Observation of rat alveolar macrophages stained with the calcium-sensitive dye Fura-2 and then treated with ufCB resulted in a rapid but transient increase in cytosolic calcium concentration in individual cells within 15 min of exposure. ufCB treatment of the primary macrophages also induced a significant increase in TNFα mRNA and protein production within 4 h of exposure. Inhibition of calcium influx using a calcium channel blocker, verapamil, as well as inhibition of calcium signalling events with an intracellular calcium chelator, BAPTA-AM, both prevented the ufCB-induced increase in TNFα protein production. TNFα mRNA production was inhibited by verapamil but not by BAPTA-AM. Addition of the antioxidant nacystelin, previously shown to inhibit ufCB-induced calcium influx into macrophages, also inhibited TNFα protein but not mRNA production. These data support the hypothesis that ultrafine particles, via reactive oxygen species, enhance calcium influx into macrophages and that these oxidative and calcium signalling events activate TNFα production.

Original languageEnglish
Pages (from-to)219-222
Number of pages4
JournalAnnals of Occupational Hygiene
Volume46
DOIs
Publication statusPublished - 2002

Keywords

  • antioxidant
  • calcium
  • macrophage
  • tumour necrosis factor
  • ultrafine particles

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health

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