Occupational exposure to carbon black nanoparticles increases inflammatory vascular disease risk: an implication of an ex vivo biosensor assay

BACKGROUND: Among manufactured or engineered nanoparticles, carbon black (CB) has largest production worldwide and is also an occupational respiratory hazard commonly seen in rubber industry. Few studies have assessed the risk for cardiovascular disease in carbon black exposed populations. An endothelial biosensor assay was used to quantify the capacity of sera from 82 carbon black packers (CBP) and 106 non-CBPs to induce endothelial cell activation ex vivo. The mediation effect of circulatory proinflammatory factors on the association between carbon black exposure and endothelial cell activation was assessed and further validated using in vitro intervention experiments. RESULTS: The average elemental carbon level inside carbon black bagging facilities was 657.0 μg/m(3), which was 164-fold higher than that seen in reference areas (4.0 μg/m(3)). A global index was extracted from mRNA expression of seven candidate biosensor genes using principal component analysis and used to quantify the magnitude of endothelial cell activation. This global index was found to be significantly altered in CBPs compared to non-CBPs (P < 0.0001), however this difference did not vary by smoking status (P = 0.74). Individual gene analyses identified that de novo expression of key adhesion molecules (e.g., ICAM and VCAM) and chemotactic factors (e.g., CCL2, CCL5, and CXCL8) responsible for the recruitment of leukocytes was dramatically induced in CBPs with CXCL8 showing the highest fold of induction (relative quantification = 9.1, P < 0.0001). The combination of mediation analyses and in vitro functional validation confirmed TNF-α, IL-1β, and IL-6 as important circulatory factors mediating the effects of carbon black exposure on endothelial cell activation responses. CONCLUSIONS: Inflammatory mediators in sera from CBPs may bridge carbon black exposure and endothelial cell activation response assessed ex vivo. CBPs may have elevated risk for cardiovascular diseases when comorbidity exists. Our study may serve as a benchmark for understanding health effects of engineered carbon based nanoparticles with environmental and occupational health relevance.