PURPOSE: Carbon nanotubes (CNT) possess novel chemical characteristics, valuable to industry, and human exposure is increasing. Useful in delivery of drugs across cell membranes, their accidental pulmonary exposure has not been carefully studied. This report assesses the cellular lung responses to a rat model of lung exposure by a single intratracheal dose of single wall CNT (SWCNT).
METHODS: With University IRB permissions, 31 outbred rats were intratracheally (i.t.) administered 500 μ g SWCNT in 50 microliters pediatric surfactant. Controls received surfactant only. Solutions of SWCNT (SES, Houston TX) were tested for sterility (< 0.03 EU LPS) to assure that effects were unrelated to microbes. Lungs were harvested at necropsy at 0.5, 3, 24 hr. Tissue was fixed and stained by hematoxylin & eosin or mucin (mucicarmine). The mucin-stained macrophages furnished an indirect method to follow SWCNT tissue movement by light microscopy. Cell counts, ELISA and Western blots were performed on BALs and tissue sections or homogenates.
RESULTS: Rapid eosinophilia (< 30 minutes) occurred in lung parenchyma of rats receiving SWCNT, also in pleural fluid at 3 hr but not in controls. Macrophages containing mucin were found in pleural fluid and the draining lymph nodes after 24 hr. ELISA demonstrated presence of a cellular damage marker (high mobility box protein 1) in BAL at all times measured. The 30 min and 3 hr damage markers and eosinophil counts were significantly related, p=0.04 Spearman correlation.
CONCLUSION: Data show airway cell contact by the i.t. SWCNT fibers releases endogenous necrotic tissue markers, stimulating the rapid influx into tissue by eosinophils normally resident in pulmonary circulation. Receptors for these damage-elicited necrotic cell proteins are also present in minutes and peak at 3 hr., the complex producing cytokine upregulation.
CLINICAL IMPLICATIONS: The rapidity of the pulmonary response to sterile nanoparticle exposure is new and important information. Early blocking of necrotic cell protein-receptor combination may be a route to taming the inflammatory cytokine sequel. This reasearch was funded by Dept. of Internal Medicine, UMKC and St. Luke’s Foundation.
DISCLOSURE: Ammar Alkhazna, No Financial Disclosure Information; No Product/Research Disclosure Information