PARENCHYMAL AND NONPARENCHYMAL LIVER-CELLS AND THEIR INTERACTION IN THE LOCAL IMMUNE-RESPONSE

Nonparenchymal liver cells (Kupffer cells, sinusoidal endothelial cells, Ito-cells and liver-associated lymphocytes) interact with hepatocytes and with each other by soluble mediators and direct cell-cell contact. The acute phase response is a nonspecific reaction of the organism to trauma, injury or infection and its main constituents the acute phase proteins are produced by hepatocytes. The profile of acute phase protein production is influenced by the local presence of cytokines with IL-6 as the principal regulator. Nonparenchymal cells (Kupffer cells, sinusoidal endothelial cells and Ito-cells) are a source of IL-6 and-therefore participate in the generation of acute phase response. The release of IL-10 by Kupffer cells with consecutive downregulation of IL-6 production may be a mechanism by which resolution of acute phase response is achieved. Still, the mechanisms underlying chronic inflammation remain unclear. Concerning the antigen-specific immune response nonparenchymal liver cells have a number of important functions. They can act as antigen-presenting cells (Kupffer cells) or mediate effector functions (liver associated lymphocytes). Local interaction of nonparenchymal cells with hepatocytes can be mediated by cytokines and/or adhesion molecule expression which again may lead to mutual influence of immunological functions, e.g. TNF-alpha release by Kupffer cells may enhance-MHC-II expression on hepatocytes and consequently augment antigen-presenting capacity leading to an improved antigen-specific immune response. Leukocytes are attracted and home to the liver by mechanisms poorly defined because the initial contact between leukocytes and macrovascular endothelium. Central to the effector function of antigen-specific lymphocytes apart from antigen-presentation is the accessory function of surrounding hepatocytes and nonparenchymal cells, which depends again on the local spectrum of cytokine and adhesion molecule expression. In chronic hepatitis different T-helper cell populations (Th1-Th2) could be found in vitro depending on the etiology of hepatitis (viral - autoimmune), which may be a reflection of different costimulatory signals. Further research involving coculture models of different sinusoidal cell populations with hepatocytes will shed light on their mutual interaction and its importance for the local immune response.