WY-14,643 [4-chloro-6-(2,3-xylidino)pyrimidinylthio-acetic acid] is a well-known non-genotoxic carcinogen and peroxisome proliferator that causes liver cancer in rodents by unknown mechanisms. Its ability to sustain elevated rates of hepatocyte DNA synthesis is most likely pivotal in the ultimate development of tumors. The source of this mitogenic stimulus following treatment of rats with WY-14...

After being delivered by the bite from an infected mosquito, Plasmodium sporozoites enter the blood circulation and infect the liver. Previous evidence suggests that Kupffer cells, a macrophage-like component of the liver blood vessel lining, are traversed by sporozoites to initiate liver invasion. However, the molecular determinants of sporozoite-Kupffer cell interactions are unknown. Understa...

Chronic inflammation drives liver cancer pathogenesis, invasion, and metastasis. Liver Kupffer cells have crucial roles in mediating the inflammatory processes that promote liver cancer, but the mechanistic basis for their contributions are not fully understood. Here we show that expression of the proinflammatory myeloid cell surface receptor TREM-1 expressed by Kupffer cells is a crucial facto...

Peroxisome proliferators are nongenotoxic rodent carcinogens that act as tumor promoters by increasing cell proliferation; however, their precise mechanism of action is not well understood. Oxidative DNA damage caused by leakage of hydrogen peroxide (H2O2) from peroxisomes was hypothesized initially as the mechanism by which these compounds cause liver tumors. It seems unlikely that oxidants of...

Kupffer cells and polymorphonuclear leukocytes (PMNs) contribute to the severe reperfusion injury of the liver after ischemia at different time points. The objective of this study was to identify the cellular source(s) of reactive oxygen formation during the PMN-induced injury phase. Kupffer cells and PMNs were isolated from the liver after 45 min of ischemia and 5 h or 24 h of reperfusion usin...

Kupffer cells are important for bacterial clearance and cytokine production during infection. We have previously shown that severe infection with Pseudomonas aeruginosa ultimately results in loss of Kupffer cells and hepatic bacterial clearance. This was associated with prolonged hepatic inflammation. However, there is a period of time during which there is both preserved hepatic bacterial clea...

BACKGROUND The role of Kupffer cells in a hepatic xenograft rejection is still unclear. We investigated the effect of blocking Kupffer cells on xenogeneic humoral injury using rat livers as the xenoperfusion models. METHODS Rat livers were perfused with fresh human blood after pretreatment either with normal saline (group 1; n = 8) or with gadolinium chloride (GdCl3) solution (group 2; n = 8)...

Kupffer cells form a large intravascular macrophage bed in the liver sinusoids. The differentiation history and diversity of Kupffer cells is disputed; some studies argue that they are derived from blood monocytes, whereas others support a local origin from intrahepatic precursor cells. In the present study, we used both flow cytometry and immunohistochemistry to distinguish 2 subsets of Kupffe...

The uptake and breakdown of formaldehyde-treated "'Ior '='I-labeled albumin in liver lysosomes have been measured in vivo. Ultracentrifuge studies and gel filtration showed that, in contrast to heat-denatured albumin frequently used in clearance experiments, our formaldehyde-treated protein did not form aggregates. Nevertheless, it was exclusively taken up in the Kupffer cells as demonstrated b...

BACKGROUND It has been proposed that PPARalpha agonists stimulate Kupffer cells in rodents which in turn, release mitogenic factors leading to hepatic hyperplasia, and eventually cancer. However, Kupffer cells do not express PPARalpha receptors, and PPARalpha agonists stimulate hepatocellular proliferation in both TNFalpha- and TNFalpha receptor-null mice, casting doubt on the involvement of Ku...