Kupfferceller

Kupffer cells are specialized macrophages located in the liver, embedded in the walls of the hepatic sinusoids, and represent the most abundant resident macrophage population in humans. They form part of the reticuloendothelial system and actively filter bacteria and debris from portal blood.

They originate during embryonic development from fetal liver monocytes and are maintained in the adult liver by self-renewal. Under inflammatory conditions they can be replenished by bone marrow–derived monocytes.

Functions include phagocytosis of pathogens, apoptotic cells, and senescent erythrocytes; clearance of circulating bacteria; expression of scavenger receptors; antigen presentation; and cytokine and chemokine production. They also participate in iron recycling from aged red blood cells via heme breakdown and ferritin release and contribute to liver tolerance to gut-derived antigens through anti-inflammatory cytokines such as IL‑10 and TGF‑β.

Phenotype and disease relevance: In humans, Kupffer cells express markers such as CD68 and CD163, and in mice they are identified by CLEC4F. They help maintain tissue homeostasis in health; however, they can polarize toward pro‑inflammatory M1 or anti‑inflammatory M2 phenotypes during injury. Chronic activation contributes to hepatic inflammation and fibrogenesis in conditions such as alcoholic liver disease, non‑alcoholic fatty liver disease, fibrosis, and cirrhosis. They are a focus of research for macrophage-targeted therapies in liver disease.