Immunohistochemical phenotyping of liver macrophages in normal and diseased human liver

Abstract

The phenotypical heterogeneity of human liver macrophages was analyzed with monoclonal antibodies that recognize antigens specific for the monocyte-macrophage lineage. Most liver macrophages in normal and diseased liver were positive for CD68, whereas fewer matured macrophages were detected by 25-F9. Comparative staining of mirror sections revealed some to be doubly positive and others to be singly CD68 positive. Quantitative analysis confirmed the difference, suggesting heterogeneity of maturation in liver macrophages. Most liver macrophages in the normal liver were negative for CD14, a receptor for lipopolysaccharide and lipopolysaccharide-binding protein complexes. Liver macrophages in liver diseases were activated to express CD14 at varying degrees and were involved in the clearance of lipopolysaccharide-lipopolysaccharide-binding protein complexes. Fc gamma RI, a receptor for monomeric IgG that is involved in antibody-mediated cell cytotoxicity, was negative in the normal liver, but was expressed in liver macrophages at inflammatory sites (e.g., in piecemeal and focal necrosis) in diseased livers. Fc gamma RII was expressed in most liver macrophages, as well as in sinusoidal endothelial cells; Fc gamma RIII was expressed in a smaller number of liver macrophages. Expression of Fc gamma RII and Fc gamma RIII was increased in chronic active hepatitis. These results suggest that liver macrophages are heterogeneous in maturation and function and that they are activated in liver diseases as shown by the novel expression of CD14 and Fc gamma RI. The restricted expression of Fc gamma RI indicates that Fc gamma RI-positive macrophages, in cooperation with cytotoxic T lymphocytes, may play an important role in liver cell injury through antibody-mediated cell cytotoxicity.

Receptor-mediated endocytosis of immune complexes in rat liver sinusoidal endothelial cells is mediated by FcγRIIb2

“…The expression of Fc␥RIII was, however, restricted to a subset of macrophages. 32 The latter study did not detect Fc␥RI in the liver. A third study, however, could only demonstrate Fc␥R expression on the placental epithelium but not on endothelial cells from other tissues.…”

Macrophages in Hepatitis B and Hepatitis C Virus Infections

“…Similarly, in HBV infection, more activated KCs expressing FasL are observed during episodes of liver damage (89), and activated KCs together with oval cells have been described in areas of inflammation and regeneration (81). Indeed, CD68 (macrophage marker) and CD14 (activated macrophages [27]) are both upregulated in viral hepatitis and correlate with liver injury (49,53,91,98). It has been proposed that in chronic HCV infection, a combination of viral (e.g., serum HCV core protein) and host (e.g., IFN-␥ and unphagocytosed endotoxins) factors cause KCs and recruited macrophages to be continuously and inappropriately activated (15).…”

CD14 upregulation as a distinct feature of non-alcoholic fatty liver disease after pancreatoduodenectomy

“…We therefore focused on CD14 expression in liver specimens from NAFLD after PD because the promoter polymorphism of CD14 has been reported as a risk factor for both alcoholic and non-alcoholic steatohepatitis [21] . CD14 expression on Kupffer cells is low in the healthy human liver [22,23] but increases in the presence of inflammatory liver disease [24] . Expression of CD14 on Kupffer cells can be upregulated with LPS [25,26] .…”