Negatively charged membrane phospholipids (PS)

Negatively charged membrane phospholipids, such as phosphatidylserine (PS), phosphatidylinositol, and phosphatidylglycerol, are essential lipid components that play critical roles in membrane structure and cell signaling (Birge et al., 2016, Cell Death & Differentiation). In healthy mammalian cells, these lipids are actively sequestered in the inner leaflet of the plasma membrane, but they become externalized on the surface of apoptotic cells and tumor-associated vascular endothelial cells (Ran and Thorpe, 2002, Int J Radiat Oncol Biol Phys). This surface exposure serves as a 'global' immunosuppressive signal in the tumor microenvironment, facilitating immune evasion (Birge et al., 2016). Therapeutic strategies, such as the monoclonal antibody bavituximab, target exposed PS to reverse this immunosuppression and induce antibody-dependent cellular cytotoxicity (Gerber et al., 2015, Clin Cancer Res). Additionally, anionic phospholipids are primary targets for certain antibiotics; for instance, daptomycin targets phosphatidylglycerol in bacterial membranes to cause depolarization (Pogliano et al., 2012, J Bacteriol). Viral envelopes also frequently expose PS, making them susceptible to PS-targeting agents that block viral entry or trigger immune clearance (Soares et al., 2008, Nat Rev Cancer).

Other names

Anionic phospholipidsAcidic phospholipidsPhosphatidylserinePhosphatidylinositolPhosphatidylglycerolPhosphatidic acidCardiolipin

Binding to externalized anionic phospholipids to trigger immune-mediated cell death (ADCC), disrupt membrane permeability, or inhibit viral entry.