Figure 12.

Induced biosynthesis of specialized LMs through M1- and M2-associated pathways. Polarization of M1 and M2 macrophages alters their ALOX pathways for the biosynthesis of proinflammatory LMs or SPMs and, thereby, regulate the initiation and resolution of neutrophilic inflammation in a time-dependent manner. In this model, exposure to inflammatogenic and fibrogenic ENMs, such as fiber-like MWCNTs, induces the production and secretion of LTB4, PGE2, and other proinflammatory LMs from M1 macrophages via induced expression of ALOX5 and ALOX5AP, which stimulates the rapid initiation of neutrophil infiltration and proinflammatory cytokine secretion. The continued presence of ENMs in the lung stimulates the production of RvD1 and other SPMs from M2 macrophages by inducing ALOX5 and ALOX15, which converts the lung environment from being proinflammatory to pro-resolving, thereby promoting the resolution of neutrophilic inflammation.