Hepatocyte nitric oxide production is induced by Kupffer cells.

To investigate the cellular communication in the liver, nitric oxide (NO) production by sinusoidal cells and hepatocytes by stimulation with cytokines and Kupffer cell-conditioned medium was quantitatively analyzed. NO production by the cells was measured by the Griess reaction, and nitric oxide synthase (iNOS) transcription level by a competitive RT-PCR assay using mutant iNOS mRNA as a standard. NO production and iNOS mRNA transcriptional levels in Kupffer cells were markedly increased by stimulation with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma), and moderately by interleukin-1beta (IL-1beta).

Role of macrophages in regeneration of liver.

In an attempt to clarify the role of macrophages and their mediators during regeneration of the liver, the difference of liver regeneration among C3H/HeN (LPS-responsive strain) and C3H/HeJ (LPS-resistant strain) mice was investigated. After a 67% partial hepatectomy, an increase in the weight of regenerating liver was significantly delayed in the C3H/HeJ mice, as compared with C3H/HeN mice. The number of hepatocytes labeled with antibody against PCNA reached maximum levels 48 hr after partial hepatectomy, but the PCNA labeling index in C3H/HeJ mice was 20% less than that for C3H/HeN mice.

Chemotactic factors released from hepatocytes exposed to acetaminophen.

To clarify the mechanism of neutrophil infiltration in the liver of acetaminophen-induced hepatic injury, chemotactic factor released from hepatocytes exposed to acetaminophen has been investigated. Hepatocytes exposed to acetaminophen release nondialyzable chemotactic factor, although acetaminophen in itself inhibits chemotaxis of neutrophils. Chemotactic activity of the nondialyzable chemotactic factor was reduced after treatment with heat (56 degrees C, 30 min) or trypsin.

Endotoxin induced cellular communication in the liver: murine models for clarification of the role of LPS-responsive macrophages in the pathogenesis of liver diseases.

In several experimental models, lipopolysaccharide (LPS) plays an important role in the pathogenesis of liver diseases. Murine models of C3H/HeN and C3H/HeJ mice have been used to elucidate the role of LPS and its responsive-macrophages in vivo, as C3H/HeN strain mice are known to be LPS-responsive, while C3H/HeJ strain mice are LPS-resistant. Furthermore, release of several kinds of biologically active mediators such as interleukin-1, tumour necrosis factor-alpha, colony stimulating factor and reactive oxygen radical is not enhanced in C3H/HeJ mice even after stimulation with LPS.

Malignant pleural mesothelioma presenting as achalasia.

A 65-year-old man with an occupational history of asbestos exposure developed dysphagia and vomiting. Clinical examinations at onset revealed a dilated esophagus with smooth narrowing at the gastroesophageal junction and no apparent tumor in and around the esophagus. Achalasia was suspected.

Modulation of ischemia-reperfusion-induced hepatic injury by Kupffer cells.

To elucidate the role of Kupffer cells in ischemia-reperfusion-induced hepatic injury, hepatic injury induced by ischemia-reperfusion was analyzed after modulation of Kupffer cell function. Ischemia of the liver was performed by occlusion of both the portal vein and hepatic artery, which enter into the left lateral and median lobes of the liver. Blood flow in the ischemic lobe was reduced, in contrast to an increased blood flow in the nonischemic lobe during occlusion of the veins.

Generation of chemotactic factor by hepatocytes isolated from chronically ethanol-fed rats.

In an attempt to clarify a mechanism of polymorphonuclear cell and/or macrophage infiltration in alcoholic liver disease, we investigated a novel chemotactic and activating factor generated by rat hepatocytes isolated from the chronically ethanol-fed rats. Hepatocytes and hepatic macrophages were isolated from rat liver by perfusion and digestion with collagenase and subsequently by differential centrifugation on a metrizamide gradient. Rat polymorphonuclear cells were prepared from blood by the dextran sedimentation and Hypaque-Ficoll technique.

Mechanism of accumulation of macrophages in galactosamine-induced liver injury: effect of lipoxygenase inhibitors on chemotaxis of spleen cells.

In an attempt to clarify a mechanism of macrophage infiltration in galactosamine-induced hepatic injury, we investigated chemotactic factor(s) generated by murine hepatocytes exposed to galactosamine. Hepatocytes, isolated from murine liver by perfusion and digestion with collagenase, were incubated with galactosamine. Conditioned medium was collected 24 h later and chemotaxis of murine spleen cells was measured by stimulation of the conditioned medium using a modified Boyden chamber.

Kupffer cell function in chronic ethanol-fed rats.

In an attempt to clarify the Kupffer cell function in alcoholism, chronic ethanol-fed rats were investigated. The clearance of latex particles in the rat was analysed to estimate the function of the reticuloendothelial system in the liver, and the phagocytic function of Kupffer cells was measured by counting particles in the cell after isolation of non-parenchymal cells by collagenase digestion of the liver following an injection of latex particles and subsequently by staining of endogenous peroxidase activities. In addition, the number of Kupffer cells and their phagocytic function were examined histologically in fresh frozen sections of liver after an injection of particles.

Oxygen-derived free radical generating capacity of polymorphonuclear cells in patients with ulcerative colitis.

Oxygen-derived free radical generating capacity of polymorphonuclear cells in 27 patients with ulcerative colitis, 10 with acute bacterial diarrhea and 20 healthy volunteers, was measured by the luminol-dependent chemiluminescence method by stimulation of formyl-methionyl-leucyl-phenylalanine. Oxidative free radical generating capacity of polymorphonuclear cells in patients with active ulcerative colitis was markedly enhanced as compared with control (p less than 0.01), while this enhanced free radical production by the cells was not detected at remission stage.

Phagocytic properties of hepatic endothelial cells and splenic macrophages compensating for a decreased phagocytic function of Kupffer cells in the chronically ethanol-fed rats.

The balance of phagocytic function among Kupffer cells, hepatic endothelial cells and splenic macrophages in the chronically ethanol-fed rats has been investigated. Clearance of latex particles in the blood was measured to estimate the function of the reticuloendothelial system. Phagocytosis of latex particles by Kupffer cells, hepatic endothelial cells or splenic macrophages in vivo was measured by counting the number of ingested particles in a cell after isolation of hepatic nonparenchymal cells or spleen cells following injection of different amounts of latex particles.

Modulation of hepatotoxicity by macrophages in the liver.

In an attempt to elucidate the role of hepatic macrophages in liver injury, we investigated galactosamine-treated rats (500 mg per kg body weight). The rats received an i.v.

Kupffer cells inhibit the lymphoproliferative response to antigenic stimulation by rat hepatocytes.

Sprague-Dawley rats were immunized with liver-specific protein. Kupffer cells and hepatocytes were prepared by the enzyme digestive procedure, and macrophage-depleted lymphocytes were prepared by the glass adherence method. Lymphocytes were incubated with macrophages or with Kupffer cells during the antigenic stimulation of mitomycin-C-treated hepatocytes for 90 h, and 3H-thymidine incorporation of lymphocytes was analyzed.