Cell Heterogeneity Within the Hepatic Lobule (Quantitative Histochemistry)

Shank, Robert E.; Morrison, George R.; Cheng, Chuan Huan; Karl, Irene E.; Schwartz, Ruth

doi:10.1177/7.4.237

Cited by 166 publications

(50 citation statements)

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“…Measurements of enzyme markers in the populations are in good agreement with previous reports on the zonal distribution (15,22) Metabolites of A 0 in the fluorescent cell population were also analyzed (Fig. 4).…”

Section: Discussionsupporting

confidence: 90%

“…To identify sorted cells, enzyme activities, whose different acinar localisation had been previously determined, mainly by histochemical techniques (15,18,22), were measured. Hepatocytes from zone 1 exhibit higher activities of succinate-dehydrogenase and pglucuronidase, whereas 5'-nucleotidase is slightly enriched in cells from zone 3. No difference in glucose-6-phosphatase was seen (Table 1).…”

Section: Cell Separation By Flow Cytometry Analysis Of Isolated Cellsmentioning

confidence: 99%

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Separation of hepatocytes of different acinar zones by flow cytometry

et al. 1989

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Hepatocytes in the proximal (zone 1) and distal (zone 3) regions of the liver acinus are selectively stained by perfusion of the isolated rat liver with 0.2–20 μM acridine orange (AO). After 10–60 min of anterograde perfusion, AO fluorescence is visible in zone 1 cells, whereas retrograde perfusion stains cells of zone 3. In this paper, we describe a technique to isolate a mixed population of fluorescent and nonfluorescent hepatocytes (cells from all acinar zones, which do not loose the zone specific AO labeling) and to separate these cells according to their zonal origin by fluorescence activated cell sorting. The zonal populations obtained were either fluorescent or non‐fluorescent (purity >95%). Separated cell fractions differed in their enzyme content (5' nucleotidase, succinate‐dehydrogenase, β‐glucuronidase). An unidentified AO metabolite, which is not found in bile after retrograde perfusion (not formed in zone 3 cells), is also absent after retrograde perfusion in sorted fluorescent cells (zone 3 cells), indicating zonal purity of sorted cells.

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Section: Discussionsupporting

confidence: 90%

Section: Cell Separation By Flow Cytometry Analysis Of Isolated Cellsmentioning

confidence: 99%

Separation of hepatocytes of different acinar zones by flow cytometry

et al. 1989

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“…Moreover, in all cirrhotic nodules examined, GLS was undetectable. This concurs with the lack of centri-DISCUSSION lobular veins in cirrhotic nodules and confirms the close topographical relation between the centrilobular microenvironOur study, confirming and extending previous results on selected enzymatic activities, [26][27][28][29][30][31][32][33][34][35][36] ammonia-metabolizing en-ment and the expression of GLS. The only marker retaining a heterogeneous distribution in cirrhosis was G6P activity, zymes, [37][38][39][40] and members of the cytochrome P450 multigene family, [15][16][17][41][42][43][44][45] shows that the human hepatic lobule presents which usually predominated at the periphery of cirrhotic nodules.…”

Section: Aid Hepa 0018supporting

confidence: 89%

The metabolic organization of the adult human liver: A comparative study of normal, fibrotic, and cirrhotic liver tissue

et al. 1996

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The mammalian hepatic lobule is characterized by a Little is known about the alterations of metabolic ormarked functional heterogeneity. [1][2][3] According to their posiganization of the human liver tissue in chronic liver distion within the hepatic lobule, hepatocytes present signifieases. We therefore compared the distribution of the folcant differences in the level of many enzyme activities, such lowing zonal metabolic markers in 10 samples of normal as those involved in the carbohydrate, ammonia, lipid, and liver tissue, 10 samples of fibrotic tissue, and 22 samples xenobiotic metabolisms, 2-5 and in the expression of some seof cirrhotic tissue: (a) the enzymatic activities of glucosecreted products, such as plasma proteins. 6 The metabolic or-6-phosphatase (G6P), lactate dehydrogenase (LDH), ganization of the mammalian hepatic lobule is well exemplisuccinate dehydrogenase (SDH), nicotinamide-adeninefied in the rat. In this species, gluconeogenesis, fatty acid dinucleotide-phosphate [NADPH] dehydrogenase (ND), oxydation, ureagenesis, and albumin synthesis predominate b-hydroxybutyrate dehydrogenase (HBDH), and glutamate dehydrogenase (GDH); (b) the protein glutamine in the periportal region of the hepatic lobule, while glycolysis, synthetase (GLS); and (c) albumin messenger RNA fatty acid synthesis, glutamine formation, and xenobiotic me-(mRNA). The normal human hepatic lobule was charac-tabolism predominate in the perivenous region. 7 The metaterized by the periportal predominance of G6P and SDH bolic zonation of the mammalian hepatic lobule is thought to enzymatic activities and albumin mRNAs, the perive-play an important physiological role by enabling the liver to nous predominance of ND and GDH, the restriction of simultaneously perform anabolic and catabolic activities, and GLS to a small perivenous compartment, and the pre-by allowing quick responses of the hepatic parenchyma to dominance of b-HBDH at the contact of both portal changes in the physiological status. 2,3,8 It is currently tracts and centrilobular veins. In fibrosis, the overall thought 2,3,8 that the maintenance of the metabolic organizametabolic organization of the normal liver tissue was tion of the liver depends mainly on microenvironmental facretained. The expression of periportal markers predomi-tors, including: (a) blood-borne factors, such as the gradients nated around enlarged portal tracts and that of perive-in oxygen, substrates, and hormones determined by the uninous markers around residual centrilobular veins. GLS directional perfusion of the hepatic lobule by the portal blood was constantly detected at the contact of centrilobular flow, (b) pericellular factors, such as the zonal differences in veins. In cirrhotic nodules, no zonation was observed the pattern of innervation, the composition of the extracellufor most enzymatic activities or for albumin. Only G6P lar matrix, and the functional characteristics of nonparenchyusually predominated at the periphery of the nodules. mal liver cells; and possibly (c) paracrine interac...

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“…Alternatively, portal areas are the site of entry of sympathetic nerve fibers into hepatic parenchyma (28); it may be that neurogenic factors mediate elements of the acute phase response (29). On the other hand, intralobular biochemical (30) or ultrastructural heterogeneity (31) may reflect differences in the capacity of peripheral and centrilobular hepatocytes to respond to the stimuli leading to CRP formation. Ultrastructural differences between these cells have been shown, e.g., human periportal cells contain more RER than do centrilobular cells (31).…”

Section: Discussionmentioning

confidence: 99%

Control of the acute phase response. Demonstration of C-reactive protein synthesis and secretion by hepatocytes during acute inflammation in the rabbit.

Kushner¹,

Feldmann²

1978

The Journal of Experimental Medicine

198

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To determine the cell of origin of C-reactive protein (CRP) and to cast light on the mechanisms leading to the acute phase response, we used an immunoenzymatic technique to visualize this protein in livers from rabbits at intervals after intramuscular injection of turpentine. CRP was detected only in hepatocytes. 8 h after turpentine injection, CRP was demonstrated in occasional periportal hepatocytes. With time, larger numbers of positive cells were detected successively in perilobular, midlobular, and centrilobular areas. On electron microscopy, CRP was detected in rough endoplasmic reticulum (RER), smooth endoplasmic reticulum (SER), and Golgi apparatus (GA). When colchicine was administered to inhibit cellular secretion of CRP, intensity of reaction and number of CRP-containing hepatocytes were substantially greater than without colchicine, but the sequence of intralobular distribution was similar. At peak serum response 38 h after turpentine injection, CRP could be demonstrated in most hepatocytes. Electron microscopic studies showed accumulation of CRP on membranes and lumina of RER, SER, GA, and in cytoplasmic vacuoles. These findings indicate that CRP is produced by progressively increasing numbers of hepatocytes after inflammatory stimulus and suggest that a mediator, acting initially in portal zones, is responsible for recruitment of cells to CRP production.

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Cell Heterogeneity Within the Hepatic Lobule (Quantitative Histochemistry)

Abstract: This investigation was undertaken to seek quantitative information concerning the relative activity of certain enzymes in hepatic cells in various parts of the lobule. The enzymes selected for study are chiefly those with important nwtabohc roles.

Cited by 166 publications

References 6 publications

Separation of hepatocytes of different acinar zones by flow cytometry

Separation of hepatocytes of different acinar zones by flow cytometry

The metabolic organization of the adult human liver: A comparative study of normal, fibrotic, and cirrhotic liver tissue

Control of the acute phase response. Demonstration of C-reactive protein synthesis and secretion by hepatocytes during acute inflammation in the rabbit.

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