observed with expression of inducible nitric oxide synthase (NOS2), which is expressed by macrophages with an anti-tumor phenotype. Functions Phagocytosis The primary function of scavenger receptors is to regulate phagocytoseis of pathogens, but they also participate in cell–cell recognition and initiation of inflammatory responses. MARCO, being a PRR, is able to bind to a wide variety of bacteria, making it an important receptor for activating an immune response against bacteria. Soluble LPS and entire bacteria can each bind bind to MARCO, as well as acetylated LDL (AcLDL), oxidized LDL (OxLDL), B cells in the marginal zone of the spleen, and apoptotic cells. MARCO is therefore able to recognize and phagocytose pathogens and apoptotic cells, and operates independently of opsonization. Regulation of Inflammation MARCO does not directly cause an inflammatory response, but it can interact with PAMPs to promote inflammation. One way MARCO does this is by tethering a pathogen to other receptors on the cell, including PRRs such as TLR2, which then lead to the activation of the transcription factor NF-κB, which regulates expression of genes that encode cytokines. Through phagocytosis, MARCO also brings pathogens into the cell, which are processed by intracellular compartments that contain other signaling receptors such as TLR3, NOD2, and NALP3. However, lung cancer cells polarize macrophages to express MARCO and acquire an immune-suppressive phenotype, through the release of IL37. MARCO-expressing TAMs blocked activation of cytotoxic T cells and NK cells, inhibiting their proliferation, cytokine production, and tumor-cell killing capacity. Furthermore, MARCO+ macrophages increased proliferation of T-regulatory (Treg) cells and production of IL10, and diminished activity of CD8+ T cells. Blocking MARCO or knocking out IL37 in lung cancer cell lines repolarized TAMs, resulting in recovered cytolytic activity and anti-tumor effects of natural killer (NK) cells and T cells, as well as reduced Treg-cell activities. Association with diseases Alzheimer's disease The activity of MARCO on microglia, the macrophages of the brain, is believed to be altered in development of Alzheimer's disease. One primary characteristic of Alzheimer's disease is the presence of numerous senile plaques in the brain that contain amyloid beta peptides (Aβ). Initially, the microglia clear the Aβ, which binds to receptors such as MARCO. During development of Alzheimer's disease, however, the ability of microglia to clear Aβ is decreased, resulting in Aβ accumulation, which is neurotoxic. MARCO also interacts with formyl peptide receptor 2 (FPR2) to form a complex that causes the microglia to