Kupffer cells are amoeboid in character, with surface features including microvilli, pseudopodia and lamellipodia, which project in every direction.

Kupffer cells also contain rough endoplasmic reticulum, a nuclear envelope, and annulate lamellae, all of which demonstrate peroxidase activity.

Because of this detection system, Kupffer cells play a critical role in initiating and mediating immune responses to bacterial infection of the liver.

Unlike other tissue macrophages, which must be continually renewed by circulating monocytes, these monocyte-derived Kupffer cells are capable of self-renewal once a population is established.

A time frame of 14 to 21 days for complete replenishment of Kupffer cell populations has been demonstrated in animal studies.

Despite high monocyte influx and maturation rates, hepatic Kupffer cell populations are tightly maintained.

[4][7][3] The primary function of the Kupffer cell is to remove foreign debris and particles that have come from the hepatic portal system when passing through the liver.

They are important for host defense and play a role in the metabolism of many different compounds including, lipids, protein complexes and small particles.

Cells in the periportal zone are directly exposed to bloodflow, and express greater lysosomal activity to more efficiently process incoming foreign substances.

In contrast, cells in the centrilobular zone experience less perfusion, and are equipped with greater stores of superoxide to combat deeply-penetrating injuries and infections.

In response to infection or irritation, Kupffer cells can produce inflammatory cytokines, TNF-alpha, oxygen radicals, and proteases.

A large amount of reactive oxygen species, pro-inflammatory cytokines and chemokines are produced by the activated Kupffer cells which lead to liver injury.

This in turn activates the transcription of pro-inflammatory cytokines and tumor necrosis factor-alpha (TNFα), with concurrent production of superoxides.

Cytokines and superoxides go on to cause inflammation and oxidizing damage respectively, while TNFα triggers the stellate cells in the liver to initiate collagen synthesis.