Polarization of Immune Cells in the Pathologic Response to Inhaled Particulates

Resolution of Pulmonary Inflammation Induced by Carbon Nanotubes and Fullerenes in Mice: Role of Macrophage Polarization

“…Inflammation is a common, early response to exposure to ENMs like CNTs in the lung. If unresolved, pulmonary inflammation may evolve into chronic and progressive disease conditions, including fibrosis and malignancy (5,7,9,35,42). In these scenarios, acute inflammation is immediately FIGURE 9 | M1-M2 polarization in lungs exposed to MWCNTs or C60F.…”

“…However, pulmonary clearance of inhaled particles and nanoparticles is often inefficient, and deposits of particulates may persist in the lung parenchyma and, in the case of asbestos fibers and certain MWCNTs, the pleural space, for a long period of time. As a result, resolution of inflammation induced by inhaled particulates is often incomplete and prolonged, which stimulates the development of granulomatous inflammation, fibrosis, lung cancer, and pleural plague and mesothelioma (35,42). Although the inflammatory and fibrotic effects of CNTs and some other ENMs have been well documented (3,4,11,52), how CNTand other ENM-induced pulmonary inflammation is resolved remains unstudied.…”

“…Macrophages play a central role in resolution by orchestrating acute inflammation toward recovery. Macrophages are actively involved in the clearance of pathogenic microorganisms and non-microbial particles, including mineral particulates and ENMs, and the efferocytosis of leukocytes and damaged tissue during pulmonary inflammation (33)(34)(35). Upon activation by microbial or sterile stimuli, macrophages polarize to subgroups that exhibit distinctive phenotypes and perform specific functions in an inducer-, time-, and context-dependent manner, though certain plasticity in the subtypes and functions of polarized macrophages has been described (37,39).…”

“…Clearance of apoptotic neutrophils by phagocytosis is known as efferocytosis. Macrophages are actively involved in the clearance of pathogenic microorganisms and non-biological particles, as well as apoptotic leukocytes and damaged tissue cells and, therefore, are a central component in the resolution of acute inflammation (33)(34)(35). Recent studies have highlighted the importance of specific subsets or reprogramming states of macrophages during inflammation initiation and progression (36,37).…”

“…We have previously shown that MWCNTs stimulate the M1 and M2 polarization of macrophages in exposed lungs to regulate the initiation and resolution of acute inflammation, which, nonetheless, leads to chronic progression to fibrosis. This dynamic evolvement from proinflammatory to pro-resolving but ultimately profibrotic development likely reflects a time-dependent progression from type 1 to type 2 inflammation prior to progression to fibrosis (12,13,35,(40)(41)(42). Whether pulmonary exposure to CNTs and other ENMs alters the pathways for the synthesis of proinflammatory LMs and SPMs and, if so, whether CNTinduced M1 and M2 polarization affects the production of SPMs and resolution of inflammation in the lung, have not been examined.…”