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

Weiden MD; Naveed B; Kwon S; Segal LN; Cho SJ; Tsukiji J; Kulkarni R; Comfort AL; Kasturiarachchi KJ; Prophete C; Cohen MD; Chen L-C; Rom WN; Prezant DJ; Nolan A
PLoS One 2012 Jul; 7(7):e40016
BACKGROUND: The WTC collapse exposed over 300,000 people to high concentrations of WTC-PM; particulates up to approximately 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-PM(10-53) or WTC-PM(2.5) 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 PM(10-53) and PM(2.5). GM-CSF clustered with IL-6 and IL-12(p70) at baseline, after exposure to WTC-PM(10-53) and in sera of WTC dust-exposed subjects (n = 70) with WTC lung injury. Similarly, MDC clustered with GRO and MCP-1. WTC-PM(10-53) consistently induced more cytokine release than WTC-PM(2.5) at 100 µg/mL. Individual baseline expression correlated with WTC-PM-induced GM-CSF and MDC. CONCLUSIONS: WTC-PM(10-53) induced a stronger inflammatory response by human AM than WTC-PM(2.5). 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.
Medical-monitoring; Respiratory-system-disorders; Emergency-responders; Rescue-workers; Hazardous-materials; Hazardous-waste-cleanup; Airborne-dusts; Airborne-particles; Particulate-dust; Particulates; In-vitro-studies; In-vivo-studies; Pulmonary-system; Lung-cells; Lung-irritants; Cytochemistry; Cytotoxic-effects; Lung-disorders; Alveolar-cells; Risk-factors; Immune-reaction; Biomarkers; Bioassays; Serology; Humans; Dust-exposure; Cellular-function; Cellular-reactions
Anna Nolan, Division of Pulmonary, Critical Care and Sleep, New York University, School of Medicine, New York, NY, USA
Publication Date
Document Type
Journal Article
Email Address
Funding Type
Grant; Cooperative Agreement
Fiscal Year
Identifying No.
Grant-Number-R01-OH-008280; Cooperative-Agreement-Number-U10-OH-008242; Cooperative-Agreement-Number-U10-OH-008243
Issue of Publication
Source Name
Public Library of Science One
Performing Organization
New York University School of Medicine
Page last reviewed: March 25, 2022
Content source: National Institute for Occupational Safety and Health Education and Information Division