Roles of Kupffer Cells in Liver Transplantation

Abstract

Kupffer cells, the resident macrophages of the liver, not only exert phagocytosis but also excrete proinflammatory cytokines. Large amounts of cytokines, produced by activated Kupffer cells, can induce aggravate liver ischemia/reperfusion (I/R) injury. Also, Kupffer cells that express protective genes protect from I/R injury after liver transplantation. Due to their key location, Kupffer cells might function as antigen-presenting cells and participate in transplantation immunity. They also seem to play a key role in innate immune responses and host defence through the expression and secretion of soluble inflammatory mediators. With this review we want to assist in improving the understanding of the contribution of Kupffer cells in liver I/R injury and the development of the transplantation immune. We hope that the delineation of the complex mechanisms of dysregulation may inspire the design and development of novel treatment approaches.

Primary non‐function is frequently associated with fatty liver allografts and high mortality after re‐transplantation

“…Additionally, cellular, biochemical and signalling processes are disturbed in hepatic steatosis with mitochondrial dysfunction and ER stress influencing the process of regeneration . Therefore, several mechanisms affected steatotic allografts during I/R‐injury . Given that these detrimental but mostly unavoidable processes run in parallel, it is of no surprise that clinical biochemistry alert to significant hepatocellular injury during the first 48 hours (Figure , panel D1 as an example of an intra‐operative biopsy demonstrating the significant reperfusion injury).…”

“…22 Therefore, several mechanisms affected steatotic allografts during I/R-injury. 13,[23][24][25] Given that these detrimental but mostly unavoidable processes run in parallel, it is of no surprise that clinical biochemistry alert to significant hepatocellular injury during the first 48 hours (Figure 2, panel D1 as an example of an intraoperative biopsy demonstrating the significant reperfusion injury).…”

Bone marrow-derived and resident liver macrophages display unique transcriptomic signatures but similar biological functions

“…Kupffer cells (KCs), the resident tissue macrophages of the liver have a crucial role in both the pathogenesis and the resolution of various liver diseases and inflammatory states including alcohol-induced liver injury [1] , non-alcoholic fatty liver disease associated with obesity [2] , ischemia reperfusion injury [3] , immune tolerance to organ transplantation [3] and infectious disease [4] .…”

“…Although once infiltrated, monocytes begin differentiating into cells that are similar to the macrophages in the tissue that they reside in [18] , the function of these bone marrow (BM)-derived monocytes once they are present in the tissue has not been fully investigated. Given that KCs are implicated in the pathogenesis and the resolution of a number of liver diseases [2] , [3] , [4] , [19] , [20] , [21] and their phagocytic capacity makes them an easy target for particle based therapeutics [22] , a greater understanding of KC biology and heterogeneity will facilitate the development of targeted liver therapeutics. Understanding whether distinct functions can be attributed to KCs of different origin will also be important for the design of new anti-infective strategies.…”

Acquiring Kupffer Cells in Mice Using a MACS-Based Method

“…K UPFFER CELLS (KCs) play an essential role in maintaining innate immunity and secondary immunity in liver [1]. KCs serve as the nurse and gatekeeper for homeostatic liver regeneration [2,3].…”