Kupffer cell depletion associated with capillarization of liver sinusoids in carbon tetrachloride-induced rat liver cirrhosis

Lough, John; Rosenthall, Léonard; Arzoumanian, Artin; Goresky, Carl A.

doi:10.1016/s0168-8278(87)80572-x

Cited by 34 publications

(24 citation statements)

References 19 publications

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“…Kupffer cells do not function normally when biliary obstruction occurs. In agreement with previous reports for obstructive jaundice and chronic CCl 4 administration, 49,50 we found that Kupffer cells were depleted on induction of liver cirrhosis. Although these cells have higher AChE levels than hepatocytes, it is unlikely that Kupffer cells contribute much to liver AChE activity, because they represent less than 15% of total liver cells.…”

Section: Discussionsupporting

confidence: 93%

Changes in liver and plasma acetylcholinesterase in rats with cirrhosis induced by bile duct ligation

et al. 2006

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Classical studies of cholinesterase activity during liver dysfunction have focused on butyrylcholinesterase (BuChE), whereas acetylcholinesterase (AChE) has not received much attention. In the current study, liver and plasma AChE levels were investigated in rats with cirrhosis induced after 3 weeks of bile duct ligation (BDL). BDL rats showed a pronounced decrease in liver AChE levels (ϳ50%) compared with sham-operated (non-ligated, NL) controls; whereas liver BuChE appeared unaffected. A selective loss of tetrameric (G 4 ) AChE was detected in BDL rats, an effect also observed in rats with carbon tetrachloride-induced cirrhosis. In accordance, SDS-PAGE analysis showed that the major 55-kd immunoreactive AChE band was decreased in BDL as compared with NL. A 65-kd band, attributed in part to inactive AChE, was increased as became the most abundant AChE subunit in BDL liver. The overall decrease in AChE activity in BDL liver was not accompanied by a reduction of AChE transcripts. The loss of G 4 was also reflected by changes observed in AChE glycosylation pattern attributable to different liver AChE forms being differentially glycosylated. BDL affects AChE levels in both hepatocytes and Kupffer cells; however, altered AChE expression was mainly reflected in an alteration in hepatocyte AChE pattern. Plasma from BDL rats had approximately 45% lower AChE activity than controls, displaying decreased G 4 levels and altered lectin-binding patterns. In conclusion, the liver is an important source of serum AChE; altered AChE levels may be a useful biomarker for liver cirrhosis. (HEPATOLOGY 2006; 43:444-453.)

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Section: Discussionsupporting

confidence: 93%

Changes in liver and plasma acetylcholinesterase in rats with cirrhosis induced by bile duct ligation

et al. 2006

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“…In addition, it has been reported that a reduction in the number of Kupffer cells and their function was observed in LC (3,24,29,33). From these reports, it was presumed that a reduction in the number and function of Kupffer cells in LC leads to impaired NK cell differentiation and maturation.…”

Section: Discussionmentioning

confidence: 99%

Liver‐Associated Natural Killer Activity in Cirrhotic Rats

Shirachi

Sata

Miyajima

et al. 1998

Microbiology and Immunology

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An impaired host defense mechanism is well known in patients with liver cirrhosis (LC). Using a sinusoidal lavage method, lymphocytes were obtained from LC rats that were administered thioacetamide, and natural killer (NK) activity was measured by 5lCr‐release assay. The NK cell count was measured by flow cytometric analysis using monoclonal antibody (Mab) 3.2.3 and/or CD 3‐8+ as markers for NK cells, and by immunohistochemical staining using Mab 3.2.3. Furthermore, interferon (IFN) α was administered to LC rats and the subsequent changes in hepatic NK activity and NK cell count were observed. In the large granular lymphocyte (LGL)‐rich fraction (Fr.1, LGLs: 60‐90%), the NK activity was significantly lower in the LC rats (40.0±3.8%) compared to that in the control rats (48.4±4.3%) (P<0.005). In addition, the number of NK cells in the liver tissues of the LC rats was significantly lower compared to that in the liver tissues of the control rats by morphometric analysis (P<0.05). For LC rats, NK activity of the Fr.1 24 hr after IFNα administration (5×104 IU / 100 g body weight) increased significantly (P<0.005). Hepatic NK activity and NK cell count were reduced in the LC rats, and recovered following IFNα administration. The results obtained in this study may give clues to better understanding the impaired host defense mechanism in LC patients.

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“…This ability of albumin-bound compounds to quickly leave the vascular space and enter the extravascular extracellular space of Disse is an important component of the hepatic uptake mechanism. Cirrhosis is characterized by “capillarization” of hepatic sinusoids with loss of fenestrations (76,106). Indicator dilution studies performed in cirrhotic patients revealed a loss of accessibility of albumin to the Space of Disse and corresponding reduced extraction of indocyanine green (ICG) (76).…”

Section: Hepatic Vascular Anatomy Facilitates Hepatocyte Transportmentioning

confidence: 99%

Organic Anion Uptake by Hepatocytes

Wolkoff

2014

Comprehensive Physiology

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Many of the compounds taken up by the liver are organic anions that circulate tightly bound to protein carriers such as albumin. The fenestrated sinusoidal endothelium of the liver permits these compounds to have access to hepatocytes. Studies to characterize hepatic uptake of organic anions through kinetic analyses, suggested that it was carrier-mediated. Attempts to identify specific transporters by biochemical approaches were largely unsuccessful and were replaced by studies that utilized expression cloning. These studies led to identification of the organic anion transport proteins (oatps), a family of 12 transmembrane domain glycoproteins that have broad and often overlapping substrate specificities. The oatps mediate Na+-independent organic anion uptake. Other studies identified a seven transmembrane domain glycoprotein, Na+/taurocholate transporting protein (ntcp) as mediating Na+-dependent uptake of bile acids as well as other organic anions. Although mutations or deficiencies of specific members of the oatp family have been associated with transport abnormalities, there have been no such reports for ntcp, and its physiologic role remains to be determined, although expression of ntcp in vitro recapitulates the characteristics of Na+-dependent bile acid transport that is seen in vivo. Both ntcp and oatps traffic between the cell surface and intracellular vesicular pools. These vesicles move through the cell on microtubules, using the microtubule based motors dynein and kinesins. Factors that regulate this motility are under study and may provide a unique mechanism that can alter the plasma membrane content of these transporters and consequently their accessibility to circulating ligands.

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Kupffer cell depletion associated with capillarization of liver sinusoids in carbon tetrachloride-induced rat liver cirrhosis

Cited by 34 publications

References 19 publications

Changes in liver and plasma acetylcholinesterase in rats with cirrhosis induced by bile duct ligation

Changes in liver and plasma acetylcholinesterase in rats with cirrhosis induced by bile duct ligation

Liver‐Associated Natural Killer Activity in Cirrhotic Rats

Organic Anion Uptake by Hepatocytes

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