WTC dust induces GM-CSF in serum of FDNY rescue workers with accelerated decline of lung function and in cultured alveolar macrophages.
Naveed-B; Comfort-AL; Ferrier-N; Segal-LN; Kasturiarachchi-KJ; Kwon-S; Chen-LC; Gordon-T; Cohen-MD; Prophete-C; Rom-WN; Prezant-DJ; Nolan-A; Weiden-M
Am J Respir Crit Care Med 2011 May; 183(Meeting Abstracts):A4770
RATIONALE: The destruction of the World Trade Center (WTC) led to a significant particulate exposure in 13,954 FDNY rescue workers. Symptomatic individuals with subsequent subspecialty pulmonary evaluation had obstruction as their predominant physiology. Utilizing a case cohort study, we propose to identify proteins in the serum of FDNY rescue workers obtained within 5 months of 9/11/2001. A cell culture model will be established using human alveolar macrophages (AM) exposed to WTC particulates. Induced biomarkers may identify pathways that regulate lung injury after an irritant exposure. METHODS: In vivo: Baseline cohort (N=801, 47% of 1720) was chosen based on the following: never smokers, male, accurate NHANES normative data, post-9/11 FDNY PFTs within 200 days of 9/11/01, and normal FEV1% predicted pre-9/11. WTC-exposed FDNY personnel with accelerated decline in lung function were identified based on FEV1% at the time of subspecialty PFT (Cases, N=100). Random controls (N=171) were chosen after stratification based on BMI and FEV1. Serum aliquots were stored at -80 degrees C. In vitro: AM obtained by bronchoalveolar lavage (BAL; N=5 subjects) were plated at 1x10(6) cells/mL overnight and then exposed to 100 microg/mL suspensions of WTC and South Bronx (SB) PM. Media alone (MA) used as the negative control and 40 ng/mL of LPS was the positive control. Supernatants and serum analyzed by Luminex on Cytokine Panel I (Millipore). RESULTS: Cases and controls had similar patterns of exposure, age at 9/11, years of service and time between exposure and serum collection. Significant elevations of sCD40L, VEGF, GM-CSF were seen in the serum of the cases. Ex vivo exposure of human AM to WTC particulates led to significant elevations in Fit-3-ligand, GM-CSF and IL-12(p40). There was a trend toward significance in TNF-alpha, IL-6 and MIP-1beta when compared with effects from equal amounts of PM(2.5) from the South Bronx. CONCLUSIONS: GM-CSF was elevated in the serum of firefighters with accelerated lung decline and in human AM stimulated ex-vivo with WTC PM. This raises the possibility that cytokines produced by AM may have driven the decline of lung function seen after exposure to WTC dust. We will confirm this finding with a case control study comparing the 100 most-affected firefighters to a representative cohort control of 171.
Particulates; Particulate-dust; Employee-exposure; Fire-fighters; Emergency-responders; Rescue-workers; Airborne-particles; Airborne-dusts; Respiratory-system-disorders; Pulmonary-system-disorders; Lung-disorders; Proteins; Biomarkers; Pulmonary-function; Cell-cultures; Cell-culture-techniques; Alveolar-cells; Lung-cells; Blood-serum; In-vitro-study; In-vivo-study; Cytotoxicity
A. Nolan, New York University School of Medicine, New York, NY
Cooperative Agreement; Grant
Cooperative-Agreement-Number-U10-OH-008243; Cooperative-Agreement-Number-U10-OH-008242; Grant-Number-R01-OH-008280
American Journal of Respiratory and Critical Care Medicine
New York City Fire Department