Editing Kupffer cell (section)

== Function ==
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. It is possible for the Kupffer cells to take in large particles by [[phagocytosis]] and smaller particles via [[pinocytosis]].<ref name=":2"/> Kupffer cells are integral in the innate responses of the immune system. They are important for host defense and play a role in the metabolism of many different compounds including, lipids, protein complexes and small particles. They are also useful in removing apoptotic cells from circulation.<ref name=":0" /><ref name=":1" /> 

The amount of Kupffer cells in the liver is held constant. Kupffer cells have a proliferative capacity, allowing for cell populations to replenish themselves: this is in complete contrast to monocyte-derived macrophages that have no proliferative potential. Old or defective cells are removed through apoptosis, as well as through being phagocytized by neighbouring Kupffer cells.

Kupffer cells are heterogeneous in their function, dependent on their location in the [[liver lobules]]. 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 cytokine]]s, [[TNF-alpha]], [[oxygen radical]]s, and [[protease]]s. Excessive production of these mediators is linked to the development of liver injury.<ref name=":2" />

Apart from [[phagocytosis|clearing]] bacteria, Kupffer cells are also responsible for recycling [[hemoglobin]] by destroying [[senescence|senescent]] [[red blood cell]]s through phagocytic action. The globin chains are re-used, while the iron-containing portion, [[heme]], is further broken down into iron, which is re-used, and [[bilirubin]], which is conjugated to [[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.<ref>{{cite journal | vauthors = Helmy KY, Katschke KJ, Gorgani NN, Kljavin NM, Elliott JM, Diehl L, Scales SJ, Ghilardi N, van Lookeren Campagne M | display-authors = 6 | title = CRIg: a macrophage complement receptor required for phagocytosis of circulating pathogens | journal = Cell | volume = 124 | issue = 5 | pages = 915–27 | date = March 2006 | pmid = 16530040 | doi = 10.1016/j.cell.2005.12.039 | s2cid = 15525209 | doi-access = free }}</ref>