title: Comparison of WTC dust size on macrophage inflammatory cytokine release in vivo and in vitro.
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.
  
  
  RESULTS
  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.
authors: Division of Pulmonary, Critical Care and Sleep Medicine, New York University School of Medicine, New York, New York, United States of America.
authors: Michael D
authors: MD
authors: Weiden
authors: Bushra
authors: B
authors: Naveed
authors: Sophia
authors: S
authors: Kwon
authors: Leopoldo N
authors: LN
authors: Segal
authors: Soo Jung
authors: SJ
authors: Cho
authors: Jun
authors: J
authors: Tsukiji
authors: Rohan
authors: R
authors: Kulkarni
authors: Ashley L
authors: AL
authors: Comfort
authors: Kusali J
authors: KJ
authors: Kasturiarachchi
authors: Colette
authors: C
authors: Prophete
authors: Mitchell D
authors: MD
authors: Cohen
authors: Lung-Chi
authors: LC
authors: Chen
authors: William N
authors: WN
authors: Rom
authors: David J
authors: DJ
authors: Prezant
authors: Anna
authors: A
authors: Nolan
mesh_terms: D000328:Adult; D000368:Aged; D054422:Chemokine CCL22 / Q000097:blood / Q000378:metabolism*; D004391:Dust; D060731:Emergency Responders; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000209:etiology / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010316:Particle Size; D011650:Pulmonary Alveoli / Q000166:cytology; D012307:Risk Factors; D047851:September 11 Terrorist Attacks
chemical_list: D054422:Chemokine CCL22; D004391:Dust; D016178:Granulocyte-Macrophage Colony-Stimulating Factor