Abstract
BackgroundThe 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 FindingsNormal 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.ConclusionsWTC-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.
Highlights
The destruction of the World Trade Center (WTC) led to the release of an estimated 10 million tons of dust, exposing over 300,000 rescue workers and New York City (NYC) residents to WTC particulate matter (WTC-Particulate Matter (PM)).[1,2,3,4] The concentrations of airborne and respirable WTC-PM ranged from 1–100 mg/m3.[5,6,7]
WTC-PM10–53 induced a stronger inflammatory response by human alveolar macrophages (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
Epidemiologic evidence links PM exposure to hospitalization and mortality from cardiovascular and pulmonary diseases. [10,11,12] Acute airway inflammation has been described after exposure to ambient PM and WTC-PM. [7,13,14,15] Exposure to WTC-PM has been implicated in the development of lung injury, reactive airways’ dysfunction, obstructive airway physiology and overall decline in FEV1. [2,16]
Summary
The destruction of the World Trade Center (WTC) led to the release of an estimated 10 million tons of dust, exposing over 300,000 rescue workers and New York City (NYC) residents to WTC particulate matter (WTC-PM).[1,2,3,4] The concentrations of airborne and respirable WTC-PM ranged from 1–100 mg/m3.[5,6,7]. [10,11,12] Acute airway inflammation has been described after exposure to ambient PM and WTC-PM. [7,13,14,15] Exposure to WTC-PM has been implicated in the development of lung injury, reactive airways’ dysfunction, obstructive airway physiology and overall decline in FEV1. Resident macrophages interact with the acute phase neutrophils that migrate into the alveolar space during inflammation. [18] Previous studies have shown that human alveolar macrophages (AM) and epithelial cells exposed to WTC-PM at doses of 5 and 50 mg, led to an increased production of interleukin (IL)-8 and IL-6. A 10-fold increased dose of WTC-PM led to a decline in production of these same cytokines. 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
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