Kupffer cells or Browicz-Kupffer cells are specialized macrophages located in the liver that form part of the reticuloendothelial system (aka: mononuclear phagocyte system). The cells were first observed by Karl Wilhelm von Kupffer in 1876. The scientist called them "sternzellen" (star cells or stellate cells) but thought falsely that they were an integral part of the endothelium of the liver blood vessels and that they originated from it. In 1898, after several years of research, Tadeusz Browicz identified them correctly as macrophages.

Their development begins in the bone marrow with the genesis of promonocytes and monoblasts into monocytes and then on to peripheral blood monocytes completing their differentiation into Kupffer cells.

The primary function of Kupffer cells is to recycle old red blood cells that no longer are functional. The red blood cell is broken down by phagocytic action and the hemoglobin molecule is split. The globin chains are reutilized while the iron containing portion or heme is further broken down into iron which is reutilized and bilirubin, which is conjugated with glucuronic acid within hepatocytes and secreted into the bile.

Helmy et al. identified a receptor present in Kupffer cells, the complement receptor of the immunoglobulin family (CRIg). Mice without CRIg could not clear complement system-coated pathogens. CRIg is conserved in mice and humans and is a critical component of the innate immune system.

BGS-18

• novel human Kupffer cell receptor protein.

CD14

• a marker of Kupffer cell activation by LPS. PMID: 16085180, PMID: 16045604, PMID: 12181178, PMID: 12121871
• may play an important role in the activation of LPS-induced Kupffer cells. PMID: 14627522
• Ethanol administration led to a significant synthesis of endotoxin receptor CD14 protein and its gene expression in Kupffer cells (KCs), which maybe result in the pathological changes of liver tissue and hepatic functional damages. PMID: 12632533
• expressed on the cell surface of monocytes and hepatic Kupffer cells, interacts with Gram-positive and Gram-negative bacteria. PMID: 12185442

CD68

• a marker for Kupffer cells. PMID: 16534142, PMID: 7959647
• the best marker for Kupffer cells and was expressed diffusely within the lobules in all groups. PMID: 15504057
• expressed in all liver transplants and normal livers on the majority of Kupffer cells. PMID: 12699427
• CD68 staining of simple fatty liver and normal liver showed elongated, spindle-shaped Kupffer cells diffusely distributed along the sinusoids throughout the lobules. PMID: 12118106

ED1

• ED1 and ED2 antigens have been particularly useful in the characterization of Kupffer cell subpopulations. PMID: 15051326
• specific for exudate macrophages. PMID: 12531686

ED2

• Specific Kupffer cell marker. PMID: 15883743, PMID: 15964588
• recognizing cell membrane antigens of resident macrophages, including Kupffer cells, is a Kupffer cell-membrane marker. PMID: 12531686, PMID: 8327856
• a resident Kupffer cell marker. PMID: 8225852

F4/80

• Resident tissue macrophages, encompassing Kupffer cells of the liver and red pulp macrophages of the spleen, characteristically express the F4/80 molecule, a cell surface glycoprotein related to the seven transmembrane-spanning family of hormone receptors. PMID: 12391169
• Kupffer cells expressed F4/80. PMID: 8697146
• The antigen is observed on all known macrophage populations (including Kupffer cells and bronchoalveolar macrophages) and is absent from any cell types that are definitely not mononuclear phagocytes. PMID: 6524692

Fucose Receptor

• Kupffer cell lectin, is a Kupffer-cell selective marker. PMID: 15541921, PMID: 8619482
• functions as the galactose-particle receptor on the Kupffer cell. PMID: 8166651
• the fucose lectin was shown to be uniquely present in Kupffer cells and absent in all other types of rat macrophages examined. PMID: 3711095

G6PD (glucose-6-phosphate dehydrogenase)

• G6PD activity were clearly visible in the cytoplasm and on the cytosolic side of the endoplasmic reticulum of Kupffer cells. Rat Kupffer cells abundantly possessed enzyme-cytochemically detectable G6PD activity. G6PD enzyme-cytochemistry may be a useful tool for the study of Kupffer cell functions. PMID: 12777215
• plays an important role in Kupffer cell function, especially in phagocytosis activity. PMID: 12376831

Lectin

• may be useful markers of Kupffer cells. PMID: 1333146

Lysozyme

• histochemical marker of kupffer cells. PMID: 8603489
• Kupffer cell activation marker. PMID: 8542503
• lysozyme and esterase-neutral protease activity was either unchanged or increased following infection by increasing numbers of nocardial cells. PMID: 3536752
• In the liver of both animals (porcine and bovine), Kupffer cells were positive for lysozyme, and cytoplasmic vacuoles in Ito cells were small. PMID: 17675812

TNF-α

• a marker of Kupffer cell activation. PMID: 12559181, PMID: 12105857, PMID: 11476962