FPR1

FPR1, or formyl peptide receptor 1, is a G protein-coupled receptor that plays a central role in the early stages of the innate immune response. It belongs to the formyl peptide receptor family, which detects N-formylated peptides associated with bacterial invasion and cellular damage. The canonical ligand for FPR1 is N-formyl-Met-Leu-Phe (fMLF), but a range of formylated peptides derived from bacteria and mitochondria can activate the receptor. Activation of FPR1 triggers chemotaxis and other effector responses in immune cells.

FPR1 signals primarily through Gi/o proteins, leading to inhibition of adenylyl cyclase, activation of phospholipase C, and increases in intracellular calcium. These signaling events promote neutrophil chemotaxis, degranulation, reactive oxygen species production, and the release of proinflammatory mediators. Desensitization and receptor internalization regulate responsiveness after ligand exposure. The receptor is a seven-transmembrane domain protein with extracellular regions that bind ligands and intracellular regions that engage G proteins and downstream pathways.

Expression of FPR1 is highest in circulating neutrophils and monocytes, with expression noted in some dendritic cells and nonimmune tissues under certain conditions. It functions as a sentinel receptor for infection, guiding leukocytes to sites of bacterial invasion or tissue injury. In addition to host defense, FPR1 activity is implicated in sterile inflammation and has been studied in the context of cancer and chronic inflammatory diseases, where it may influence tumor cell behavior and the inflammatory milieu.

Ongoing research aims to understand its precise roles across species and tissues and to explore FPR1 as a potential therapeutic target for modulating inflammation and immunity.