Furthermore expression of a dominant negative are involved

Therefore, regulatory control of phagocytosis is essential to limit damage to the host during pathogen clearance, and negative regulation of phagocytic activity may provide protection against SC 58125 pathological phagocytosis. Performing further studies on the specific signal transduction components that negatively regulate phagocytosis is essential. Preliminary experiments have shown that S4 cellular prion protein may play an important role in phagocytosis. PrPC is a glycosylphosphatidylinositol -anchored glycoprotein encoded by a specific prion protein gene. It is expressed mainly in the central nervous system but is also expressed in other cell types, including macrophages. PrPC can be conformationally converted into PrPSC, which accumulates in the brain in prion disease. Although a great deal has been learned about PrPSC and its role in prion propagation, the physiological functions of PrPC remain unclear. Numerous studies have suggested that PrPC may have protective functions, including providing protection against apoptotic and oxidative stress, facilitating cellular uptake or binding of copper ions, promoting transmembrane signaling, and participating in the formation and maintenance of synapses. PrPC is also necessary for neuronal survival and maintenance of the myelin sheath around peripheral nerves. Additionally, although numerous reports have revealed a relationship between PrPC and the phagocytic ability of different cell lines following ingestion of various particles, the results are conflicting. Studies have supported that Rab7a interacts with PrPC and that endosomal compartments are involved in the trafficking and regulation of PrPC ; however, further studies are required to elucidate the specific signaling mechanisms mediating the important roles of PrPC in phagocytosis. Therefore, in this study, we sought to investigate the role of PrPC during phagosome formation and maturation, and we hypothesized that PrPC may exert an important protective effect against internalized particles or pathogens. Macrophages act as the first line of protection in the innate immune response and play an important role in phagocytosis, antigen presentation, and inflammatory cytokine production. The classical activation of macrophages corresponds to the first phase, also known as the killing phase, of the innate immune response to acute stimuli and is characterized by the induction of a specific gene profile and the subsequent production of multiple cytoactive factors such as TNF-a, NO, and IL-1 that protect against tissue invaders.

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