Biological Roles of Phagoptosis in Neurological Issues, Cancer, and Aging

Inflammation can enable phagocytes to kill, despite their often restricted capacity to phagocytose live cells. Numerous phagocytic machinery components are upregulated by inflammation, which can result in increased opsonin release and expression, as well as improved phagocytic receptor activation and expression. Inflammatory signals are required to induce the intracellular activation of integrin-mediated phagocytic receptors, such as CR3 and the vitronectin receptor. Receptor desialylation may outside-in activate CR3, MERTK, and TREM2. By eliminating inhibitory SIGLEC signals, phagocyte desialylation may also start phagocytosis. Hemophagocytic lymphohistiocytosis and related inflammatory disorders are defined by the engulfment of viable B cells, T cells, and myeloid cells by macrophages that have been activated through inflammatory signaling pathways. To support the normal development of various organs, macrophages phagocytize cells undergoing "programmed cell senescence," a developmental pause in cell proliferation. In both the embryonic and adult brains, microglia regulate the number of neurons by phagocytosing neuronal precursor cells and newly formed neurons. Microglial phagocytosis of viable neurons represents a key mechanism of neuronal loss, whereby stressed, damaged, or excess neurons are selectively eliminated. Given the restricted capacity for neurogenesis in the adult brain, neuronal elimination through phagocytosis can be detrimental. Blocking phagocytosis decreases neuronal loss in animal models of stroke, traumatic brain injury, epilepsy, retinal degeneration, Parkinson's disease, and Alzheimer's disease. This suggests that microglial engulfment of viable neurons plays a role in the development of neurological disorders.