Comparison of wtc dust size on macrophage inflammatory cytokine release in vivo and in vitro

Michael D. Weiden, Bushra Naveed, Sophia Kwon, Leopoldo N. Segal, Soo Jung Cho, Jun Tsukiji, Rohan Kulkarni, Ashley L. Comfort, Kusali J. Kasturiarachchi, Colette Prophete, Mitchell D. Cohen, Lung Chi Chen, William N. Rom, David J. Prezant, Anna Nolan

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Background: The WTC collapse exposed over 300,000 people to high concentrations of WTC-PM; particulates up to ~50 mm were recovered from rescue workers' lungs. Elevated MDC and GM-CSF independently predicted subsequent lung injury in WTC-PM-exposed workers. Our hypotheses are that components of WTC dust strongly induce GM-CSF and MDC in AM; and that these two risk factors are in separate inflammatory pathways. Methodology/Principal Findings: Normal adherent AM from 15 subjects without WTC-exposure were incubated in media alone, LPS 40 ng/mL, or suspensions of WTC-PM10-53 or WTC-PM2.5 at concentrations of 10, 50 or 100 μg/mL for 24 hours; supernatants assayed for 39 chemokines/cytokines. In addition, sera from WTC-exposed subjects who developed lung injury were assayed for the same cytokines. In the in vitro studies, cytokines formed two clusters with GM-CSF and MDC as a result of PM10-53 and PM2.5. GM-CSF clustered with IL-6 and IL-12(p70) at baseline, after exposure to WTC-PM10-53 and in sera of WTC dust-exposed subjects (n = 70) with WTC lung injury. Similarly, MDC clustered with GRO and MCP-1. WTC-PM10-53 consistently induced more cytokine release than WTC-PM2.5 at 100 μg/mL. Individual baseline expression correlated with WTC-PM-induced GM-CSF and MDC. Conclusions: WTC-PM10-53 induced a stronger inflammatory response by human AM than WTC-PM2.5. This large particle exposure may have contributed to the high incidence of lung injury in those exposed to particles at the WTC site. GM-CSF and MDC consistently cluster separately, suggesting a role for differential cytokine release in WTC-PM injury. Subject-specific response to WTC-PM may underlie individual susceptibility to lung injury after irritant dust exposure.

Original languageEnglish (US)
Article numbere40016
JournalPloS one
Volume7
Issue number7
DOIs
StatePublished - Jul 18 2012

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Weiden, M. D., Naveed, B., Kwon, S., Segal, L. N., Cho, S. J., Tsukiji, J., Kulkarni, R., Comfort, A. L., Kasturiarachchi, K. J., Prophete, C., Cohen, M. D., Chen, L. C., Rom, W. N., Prezant, D. J., & Nolan, A. (2012). Comparison of wtc dust size on macrophage inflammatory cytokine release in vivo and in vitro. PloS one, 7(7), [e40016]. https://doi.org/10.1371/journal.pone.0040016