Host: The Japanese Society of Toxicology
Name : The 49th Annual Meeting of the Japanese Society of Toxicology
Date : June 30, 2022 - July 02, 2022
Carbon nanotubes (CNT), the highly representative products of nanotechnology, have been recently added to the so-called SIN (‘Substitute It Now’) list of chemicals by the international Chemical Secretariat (ChemSec), although the general toxicity of CNT is still under debate. A certain type of long needle-like multi-walled CNT (MWCNT) has been shown in numerous studies to have asbestos-like pathogenicity in lungs and mesothelium of rodent models. In both rodents and humans, MWCNT and asbestos fibers are efficiently recognized by professional phagocytes such as macrophages. However, after being tethered to the macrophage surfaces, these fibers are not easily phagocytosed and instead cause damages to the plasma membranes and/or phagolysosomal membranes. This process, called frustrated phagocytosis, induces macrophage cell death and NLRP3 inflammasome activation leading to secretion of IL-1β, a pro-inflammatory cytokine. Frustrated phagocytosis initiates inflammatory cascades involving various immune cells and fibroblasts, leading to granuloma and mesothelioma development. Therefore, it is important to understand the molecular mechanism of initial interactions between CNTs and macrophages that trigger biological responses to CNT. We have recently identified T-cell immunoglobulin mucin receptor 4 (Tim4) and Tim1 as CNT receptors. These Tim molecules are unique in that they have a cluster of aromatic residues at their apex positions to facilitate direct recognition of MWCNT and the frustrated phagocytosis. I here focus on the molecular mechanism of macrophage inflammatory responses to MWCNT.
