Effects of micro- and nanoplastic exposure on macrophages: a review of molecular and cellular mechanisms

Micro- and nanoplastics (MNPs), pervasive environmental pollutants, contaminate water, soil, air, and the food chain and ultimately accumulate in living organisms. Macrophages are the main immune cells that gather around MNPs and engulf them through the process of phagocytosis. This internalization triggers M1 polarization and the secretion of inflammatory cytokines, including IL-1, IL-18, IL-12, TNF-α, and IFN-γ. Furthermore, MNPs damage mitochondria and lysosomes, causing overactivation of iNOS and excessive production of ROS. This results in cellular stress and induce apoptosis, necroptosis, and, in some cases, metosis in macrophages. The internalization of MNPs also increases the expression of receptors, involving CD36, SR-A, LOX-1, and the macrophage receptor with a collagenous structure (MARCO) while decreasing ABCA-1 and ABCG-1. MNPs in adipose tissue macrophages trigger proinflammatory cytokine secretion, causing adipogenesis, lipid accumulation, insulin resistance, and the secretion of inflammatory cytokines in adipocytes. Various factors influence the rate of MNP internalization by macrophages, including size, charge, and concentration, which affect internalization through passive diffusion. Receptor-mediated phagocytosis of MNPs occurs directly <i>via</i> receptors like T-cell immunoglobulin and mucin domain containing 4 (TIM-4) and MARCO. The attachment of biomolecules, including proteins, antibodies, opsonins, or microbes to MNPs (forming corona structures) promotes indirect receptor-mediated endocytosis, as macrophages possess receptors like TLRs and FcγRIII. MNPs also cause gut dysbiosis, a risk factor for proinflammatory microenvironment and M1 polarization. Here, we review the mechanisms and consequences of MNP macrophage exposure, which is linked to autoimmunity, inflammation, and cardiometabolic syndrome manifestations, including atherosclerosis and obesity, highlighting the immunotoxicity of MNPs.