Thymic involution produced by diesel exhaust particles and their constituents in mice

Abstract

Epidemiological studies suggest that diesel exhaust particles (DEP) contribute to an increase in allergic diseases. To assess the effects of DEP on the central immune system, mice were exposed to DEP by intraperitoneal (IP) administration. Exposure to DEP resulted in severe thymic involution accompanied by a reduction in the number of thymocytes, especially in cortical CD4⁺CD8⁺ double positive and double negative subsets. Core carbon particles associated with a mixture of chemical compounds in DEP did not appear to be responsible for the DEP-induced thymic involution because carbon graphite does not affect neither the number nor the CD4/CD8 profile of thymocytes. Extraction of DEP by ether, acidic and basic solvents showed that several independent fractions including the neutral ether fraction, which contains polycyclic aromatic hydrocarbons (PAH), induced thymic involution. Among major PAH components of DEP, benzo[b]fluoranthene (BbF), benzo[a]pyrene (BaP), and benzo[k]fluoranthene (BkF) were very potent inducers of thymic involution at an ED50 of less than 100 ng per mouse body. Nonetheless, DEP treatment of mice with targeted disruption of genes encoding the aryl hydrocarbon receptor (AHR), AHR nuclear translocator (ARNT), or microsomal epoxide hydolase (mEH) indicated that DEP produced thymic involution even in the absence of PAH-induced AHR/ARNT signal transduction or mEH-mediated PAH catabolism. On the other hand, BaP-mediated thymic involution was completely dependent on AHR, partially dependent on ARNT in T cells, and independent of mEH. These results indicate that DEP-induced thymic involution is mediated both by PAH-AHR/ARNT-dependent and -independent mechanisms.

Keywords:

• Diesel exhaust particle
• thymic involution
• polycyclic aromatic hydrocarbon
• aryl hydrocarbon receptor
• microsomal epoxide hydrolase

Acknowledgment

This work was supported by the grants from the Ministry of Education, Science, Sports and Culture.