Fig. 9.

Graphical Summary. Consequences of MWCNT oropharyngeal exposure in C57BL/6 mice. MWCNT induced pulmonary inflammatory activation as evidenced by increased neutrophilia and dose-dependent cytokine BALF profile and whole lung gene expression. MMP blockade did not play a role in the observed pulmonary findings. However, MMP activity was shown in induce serum peptide profile changes in a dose-dependent differential manner. Administration of broad-spectrum MMP inhibitor Marimastat abrogated these serum changes and return peptide profiles to near unexposed levels. The systemic consequences of these serum changes were evaluated in vitro. Serum from MWCNT exposed mice decreased endothelial barrier integrity as assessed via ECIS. Marimastat treatment, presumably through blockade of MMP activity in the lung, resulted in serum with considerably less potential for endothelial cell activation. These findings provide a mechanism for MWCNT action in the lung and starts to elucidate the systemic consequences of inhalation exposures to MWCNT. Additionally, serum findings provide a base for the exploration of MWCNT exposure and pathological systemic consequences, as well as the identification of biomarkers of both