Comparison of WTC Dust Size on Macrophage Inflammatory Cytokine Release In vivo and In vitro

• Published in: PloS one Vol. 7; no. 7; p. e40016
• Main Authors: Weiden, Michael D., Naveed, Bushra, Kwon, Sophia, Segal, Leopoldo N., Cho, Soo Jung, Tsukiji, Jun, Kulkarni, Rohan, Comfort, Ashley L., Kasturiarachchi, Kusali J., Prophete, Colette, Cohen, Mitchell D., Chen, Lung-Chi, Rom, William N., Prezant, David J., Nolan, Anna
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18.07.2012; Public Library of Science (PLoS)
• Subjects: Adult; Aged; Air pollution; Analysis; Biology; Biomarkers; Chemokine CCL22 - blood; Chemokine CCL22 - secretion; Chemokines; Critical care; Cytokines; Differential media; Dust; Emergency Responders; Environmental health; Exposure; Female; Fire stations; Firefighters; Fires; Gene expression; Genomes; Granulocyte-macrophage colony-stimulating factor; Granulocyte-Macrophage Colony-Stimulating Factor - blood; Granulocyte-Macrophage Colony-Stimulating Factor - secretion; Granulocytes; Health services; Human behavior; Humans; Inflammation; Inflammation - blood; Inflammation - etiology; Inflammation - metabolism; Inflammatory response; Injuries; Interleukin 12; Interleukin 6; Kinases; Lipopolysaccharides; Lung diseases; Lungs; Macrophages; Macrophages - secretion; Male; Media (differential); Medicine; Middle Aged; Monocyte chemoattractant protein 1; Neutrophils; Occupational exposure; Occupational health; Particle Size; Particulate matter; Particulates; Physicians; Proteins; Pulmonary Alveoli - cytology; Risk analysis; Risk Factors; September 11 Terrorist Attacks; Sleep; Tuberculosis; New York; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0040016

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. 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. 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.