Parenchymal Cells In Primary Culture Research Articles

Uptake of FH by two types of scavenger-like receptors in rat liver parenchymal cells in primary culture.

Several anionic proteins that are known to be substrates of scavenger receptors documented in the literature were selected and tested for their effects on the uptake of fractionated heparin (FH), an anionic macromolecular drug. The tests were made in rat liver parenchymal cells to characterize scavenger-like receptors involved in FH uptake, probing into substrate recognition characteristics in comparison with those of scavenger receptors. Although the uptake of FH was completely inhibited by dextran sulfate, a typical substrate of scavenger receptors, suggesting that scavenger-like receptors that have affinity for some anionic macromolecules are responsible for the uptake, it was not inhibited by acetylated low density lipoprotein (Ac-LDL), another typical substrate. Thus, the scavenger-like receptors were suggested to be different from the major scavenger receptors of classes A and B that are known to be sensitive to Ac-LDL. The uptake of FH was only partially inhibited by maleylated bovine serum albumin (Mal-BSA), suggesting that the scavenger-like receptors can be classified into two types in terms of sensitivity to Mal-BSA. The Mal-BSA-sensitive receptor was also found to be sensitive to oxidized low density lipoprotein (Ox-LDL). Kinetic analysis revealed that the binding capacity (Bmax) of the Mal-BSA-insensitive receptor was significantly larger than that of the Mal-BSA-sensitive one, though their dissociation constants (Kd) and apparent internalization rate constants (kint,app) were comparable. Information obtained in this study should be helpful for understanding the disposition mechanism of FH and also of anionic macromolecules and for developing delivery strategies, although the physiological roles and molecular identity of each receptor need to be further clarified in the future.

Pharmacokinetic analysis of scavenger receptor-mediated uptake of mucopolysaccharides in various cells

Although the scavenger receptor-mediated uptake has been qualitatively investigated in the research fields of biochemistry and pathology, pharmacokinetic characteristics of the scavenger receptors are poorly understood. In this review, we summarized basic findings on scavenger receptors reported in available literature, and introduced our recent studies on the quantitative characteristics of the scavenger receptor-mediated uptake. High molecular weight fractionated [3H]heparin (HMWFH, 16,000-24,000 Da), one of the model mucopolysaccharides, was investigated to elucidate its uptake mechanism into isolated rat Kupffer cells, isolated peritoneal macrophages and liver parenchymal cells in primary culture. The equilibrium bindings of HMWFH to isolated Kupffer cells and peritoneal macrophages were concentration-dependent with the respective dissociation constants (Kd) of 5.7 and 6.0 nM and with the respective maximum binding capacities (Bmax) of 1.5 and 1.9 pmol/10(6) cells. Several ligands of scavenger receptors inhibited the binding of HMWFH to macrophages, suggesting the involvement of scavenger receptors in the uptake of HMWFH by these macrophages. It was also suggested that the scavenger receptor-mediated uptake is different from the receptor-mediated endocytosis of polypeptides and phagocytosis, based on the evidence of the now inhibitory effects of an inhibitor of receptor-mediated endocytosis of polypeptides(phenylarsine oxide) and phagocytosis inhibitors (cytochalasine B and colchicine) on the internalization. The involvement of scavenger-like receptors was also suggested in the uptake of HMWFH by liver parenchymal cells in primary culture by demonstrating inhibitory effects of ligands for scavenger receptors. The internalization into liver parenchymal cells by scavenger-like receptors was not affected by an inhibitor of receptor-mediated endocytosis of polypeptides and phagocytosis inhibitors, similarly to the results in the macrophage scavenger receptors. The Kd of 53.5 nM and Bmax of 32.8 pmol/10(6) cells in parenchymal cells were both in the order of magnitude larger than those in isolated Kupffer cells, suggesting the binding of HMWFH to scavenger-like receptors in parenchymal cells with lower affinity and higher capacity. On the other hand, an apparent internalization rate constant (kint, app) of 0.0056 min-1 was comparable with that in Kupffer cells (0.0118 min-1). Thus, we demonstrated the involvement of scavenger receptors in the uptake of HMWFH by rat Kupffer cells, peritoneal macrophages and liver parenchymal cells, and succeeded in characterizing the uptake kinetically. These findings should provide useful information for not only establishing the rational clinical use of mucopolysaccharides but also developing new drugs such as antiatherosclerotic agents and peptides delivered to cells with scavenger receptors.

Internalization of Fractionated 3H-Heparin by the Scavenger-Like Receptor in Rat Liver Parenchymal Cells in Primary Culture

The present study was aimed at clarifying the uptake mechanisms of fractionated 3H-heparin (FH) in rat liver parenchymal cells in an effort to explore further the clinical applications of mucopolysaccharides, including their utilization in drug delivery. The internalization and surface binding of FH were determined by removing surface-bound FH by the NaCl wash method in uptake experiments in rat liver parenchymal cells in primary culture. Initial and transient peaks were observed in the time course of the surface binding of FH, suggesting the involvement of receptor-mediated endocy tosis (RME) and downregulation of the receptors. Consistent with this suggestion, internalization of FH was reduced by lowering the temperature from 37 to 4°C, while total association was unchanged. Although the internalization of FH was slow and concentration independent, both total association and internalization were inhibited by ligands of the scavenger receptor and some anions, but not by inhibitors of the RME of polypeptides. All these results collectively suggest the involvement of the scavenger receptor or similar substance in terms of substrate specificity in the uptake of FH in rat liver parenchymal cells. This is the first suggestion of the existence of the scavenger-like receptor in liver parenchymal cells. Macromolecular compounds such as heparin have recently been increasingly investigated for their clinical applications, including utilization as carriers for drug delivery (Nishikawa et al. 1995). Although there have been a number of studies concerning the disposition of polypeptides in the body and the utilization of macromolecules as drug carriers, more extensive studies are required to exploit a variety of macromolecules for clinical applications. Heparin, a macromolecular drug with molecular weights ranging from 3000 to 30,000 d., has been used as an anticoagulant drug. The disposition of heparin after intravenous administration depends on the molecular weight

Kinetic characterization of binding and internalization of fractionated [3H]heparin in rat liver parenchymal cells in primary culture.

The binding and internalization of fractionated [3H]heparin (FH) was kinetically analyzed in rat liver parenchymal cells to clarify its cellular uptake mechanism. The binding of FH to the cell surface was saturable with the dissociation constant (Kd) of 53.5 nM and a maximum binding capacity (Bmax) of 19.9 pmol/mg protein. The binding of FH to the cell surface was competitively inhibited not only by heparan sulfate, a polyanion analogous to heparin, but also by rose bengal, an organic anion, suggesting the binding is based on an electric interaction requiring an anionic charge for substrates and consistent with the earlier suggestion of the involvement of the scavenger-like receptor. According to kinetic model analysis, the rate constants of association (K(on)), dissociation (k(off)), and internalization (k(int).app) were estimated to be 0.0005 nM-1 min-1, 0.0112 min-1, and 0.0056 min-1, respectively. Although both Kd and Bmax were larger than those reported in Kupffer cells, suggesting lower affinity and higher capacity in liver parenchymal cells, the apparent internalization rate constant was similar to that in Kupffer cells. We thus provided additional evidence suggesting that a scavenger-like receptor exists in rat liver parenchymal cells, and then kinetically characterized the surface binding and internalization of fractionated heparin by this receptor.

The role of protein kinase C in the inactivation of hepatic glycogen synthase by calcium-mobilizing agonists.

The regulation of glycogen synthase by Ca2+-mobilizing hormones was studied by using rat liver parenchymal cells in primary culture. Long-term exposure of hepatocytes to 4 beta-phorbol 12-myristate 13-acetate (TPA) resulted in a decrease in vasopressin or ATP inhibition of glycogen synthesis and glycogen synthase activity, without any change in the activation of glycogen phosphorylase. In contrast, treatment with TPA did not diminish the effects of glucagon, isoprenaline or A23187 on glycogen synthase or phosphorylase. TPA treatment for 18 h did not change specific [3H]vasopressin binding, but abolished protein kinase C activity in a concentration-dependent manner. The effects of TPA to decrease protein kinase C activity and to reverse the inactivation of glycogen synthase by vasopressin were well correlated and were mimicked by mezerein, but not by 4 alpha-phorbol. However, 1 microM-TPA totally inhibited protein kinase C activity, but reversed only 60% of the vasopressin effect on glycogen synthase. It is therefore concluded that Ca2+-mobilizing hormones inhibit glycogen synthase partly, but not wholly, through a mechanism involving protein kinase C.

The mechanism of pantothenate transport by rat liver parenchymal cells in primary culture.

The mechanism of pantothenate transport across the plasma membrane was investigated with initial velocity studies of [14C]pantothenate uptake and efflux in rat liver parenchymal cells maintained in primary culture. At 116 mM sodium, double-reciprocal plots of the initial velocity of uptake versus [pantothenate] were linear from 0.3 to 36.5 microM pantothenate and gave an apparent Km,pant of 11 +/- 2 microM. The rate of pantothenate uptake at 0 [sodium] was about 14% of the rate at 116 mM sodium, and the reciprocal of the apparent Km,pant was a linear function of [sodium]. Vmax obtained by extrapolation to infinite [pantothenate] was independent of [sodium]. Ouabain, gramicidin D, cyanide, azide, and 2,4-dinitrophenol inhibited uptake, but preloading cells with pantothenate did not. Pantothenate derivatives or carboxylic acids were only weak inhibitors of uptake. Efflux was measured in cells preloaded with [14C]pantothenate. The apparent Km for efflux was 85 +/- 29 microM, and the rate of efflux was unaffected by addition of pantothenate, sodium, ouabain, gramicidin D, or 2,4-dinitrophenol to the external medium. These features are consistent with a mechanism for pantothenate transport in which sodium and pantothenate are cotransported in a 1:1 ratio on a carrier highly specific for pantothenate; sodium decreases the apparent Km for pantothenate, and a sodium-carrier complex forms only on the intracellular side of the membrane.

Long-Term Maintenance of Functional Rat Liver Parenchymal Cells in Primary Culture

Long-Term Maintenance of Functional Rat Liver Parenchymal Cells in Primary Culture

Morphological changes in rat hepatocytes in primary culture induced by Misonidazole, desmethylmisonidazole and Ro 03-8799.

Isolated rat hepatocytes in early primary culture were incubated in the presence of three substituted nitroimidazoles currently of clinical interest as tumour radiosensitisers. The effects of 3h treatments with Misonidazole (MISO), Desmethylmisonidazole (DESMISO) and the basic compound Ro 03-8799 were monitored both directly from treatment and following a 24h 'recovery' period. Morphological changes were observed by SEM and TEM and included effects on the plasma membrane and the nucleus. The plasma membrane of DESMISO and 03-8799 treated cells was characterised by blebbed regions not present in control cultures, and considered indicative of an early toxic insult. Blebs were most evident in 03-8799 treated hepatocytes where they often contained coils of endoplasmic reticulum within the ground plasma. Blebbed areas were less evident 24h after the removal of the drugs from surviving cells. An increased aggregation of peripherally located heterochromatin within the nucleus was the other main morphological alteration induced by nitroimidazole treatment. This was again more prevalent in 03-8799 and DESMISO exposures; and particularly in cells demonstrating membrane damage. Parallel viability studies indicated an efficacy of the nitroimidazole towards rat liver parenchymal cells in primary culture of Ro 03-8799 greater than DESMISO greater than MISO. This fitted the order predicted from the morphological findings and from previously published clinical data. The validity of monitoring structural parameters as a means of initially indicating lesion sites following drug treatments in the hepatocyte cytotoxic screening model is considered.

Xenopus fibrinogen. Characterization of subunits and hormonal regulation of biosynthesis.

In this paper we describe the purification and characterization of Xenopus plasma fibrinogen and the hormonal factors which regulate synthesis and secretion of fibrinogen in liver parenchymal cells in primary culture. As in other vertebrate species, Xenopus fibrinogen is composed of three nonidentical polypeptide chains, A alpha, B beta, and gamma. In contrast to mammalian fibrinogens, the B beta chain of Xenopus fibrinogen has a higher apparent molecular weight than the A alpha chain. The gamma chain has the lowest molecular weight in the frog protein, as in that of other species. The relatively large size of the frog B beta chain results from the unusually large size of the NH2-terminal B fibrinopeptide, which is released by thrombin cleavage of fibrinogen. Hormonal regulation of fibrinogen biosynthesis was examined using a primary cell culture system. Purified Xenopus liver parenchymal cells, maintained for several weeks in a defined culture medium, gradually decrease the synthesis and secretion of fibrinogen. Sustained production of this protein is dependent upon the addition of a glucocorticoid, dexamethasone, to the culture medium. Fibrinogen production is suppressed if an estrogen, estradiol-17 beta, is added to the culture medium together with dexamethasone and triiodothyronine. The Xenopus system provides new insight into the structure of fibrinogen, the evolution of this protein, and the hormonal factors which regulate its synthesis.

Kinetic aspects of hemoglobin.haptoglobin-receptor interaction in rat liver plasma membranes, isolated liver cells, and liver cells in primary culture.

125I-Hemoglobin.haptoglobin injected intravenously into rats was incorporated into liver parenchymal cells as evidenced by a cell separation technique. A mixture of freshly isolated liver parenchymal and nonparenchymal cells failed to internalize and degrade the 125I-hemoglobin.haptoglobin added, although it retained the ability to bind the molecule. The liver parenchymal cells in primary culture also lacked the ability to degrade 125I-hemoglobin.haptoglobin, although they bound the molecule more extensively as compared with the freshly isolated liver cells. It was confirmed that the 125I-hemoglobin.haptoglobin which was bound to the freshly isolated liver parenchymal cells localized on the outer surface of liver plasma membranes. Scatchard plots revealed the existence of two binding sites for 125I-hemoglobin-haptoglobin on the isolated liver plasma membrane: an apparent high affinity binding site (Kd = 1.3 X 10(-7) M) and an apparent low affinity binding site (Kd = 4.0 X 10(-6) M) at 37 degrees C. In contrast, freshly isolated liver parenchymal cells had only an apparent low affinity binding site (Kd = 1.4 X 10(-6) M) at 37 degrees C. Impairment of the apparent high affinity binding site during the isolation procedure with collagenase seemed to be related to loss of the ability to internalize and degrade the 125I-hemoglobin.haptoglobin molecules into the freshly isolated liver parenchymal cells or liver parenchymal cells in primary culture.

Active synthesis of glycosaminoglycans by liver parenchymal cells in primary culture

Rat liver parenchymal cells were evaluated after 2 days of primary culture for their ability to synthesize and accumulate heparan sulfate as the major component and low-sulfated chondroitin sulfate, dermatan sulfate, chondroitin sulfate and hyaluronic acid as the minor ones. The newly synthesized glycosaminoglycans secreted into the medium were different from those remaining with and/or on the cell layer. Low-sulfated chondroitin 4-sulfate, a major glycosaminoglycan in blood, was synthesized in the order of 320 μg/liver per day, more than 90% of which was secreted into the medium within 16 h and 40% of the glycan secreted was degraded during that time. On the other hand, heparan sulfate, the major glycosaminoglycan synthesized by the parenchymal cells, was mainly distributed in the cell layer. After 8 days of culture, the synthesis of glycosaminoglycans by the cells increased markedly, especially dermatan sulfate, chondroitin sulfate and hyaluronic acid.

Gluconeogenesis in rat liver parenchymal cells in primary culture: permissive effect of the glucocorticoids on glucagon stimulation of gluconeogenesis.

Primary cultures of parenchymal cells isolated from adult rat liver by a collagenase perfusion procedure and maintained as a monolayer in a serum-free culture medium were used to study gluconeogenesis and the role that the glucocorticoids play in the control of this pathway. These cells carried out gluconeogenesis from three-carbon precursors (alanine and lactate) in response to glucagon and dexamethasone added alone or in combination. Maximum glucose production was observed with cells pretreated for several hours with dexamethasone and glucagon prior to addition of substrate and glucagon (8- to 12-fold increase over basal glucose production). Half-maximum stimulation of gluconeogenesis was seen with 3.6 X 10(-10) M glucagon and 3.6 X 10(-8) M dexamethasone. Maximum stimulation was observed with 10(-7) M glucagon and 10(-6) M dexamethasone. The length of time of dexamethasone pretreatment was found to be important in demonstrating the effect of glucocorticoids on glucagon-stimulated gluconeogenesis. Treatment of cells with dexamethasone for 2 hours did not result in an increase in glucose production over identical experimental conditions in the absence of dexamethasone, whereas pretreatment for 5 hours (1.2-fold increase) or 15 hours (1.7-fold increase) did result in an increase in glucose production. The results establish that the adult rat liver parenchymal cells in primary culture are a valid model system to study hepatic gluconeogenesis. In addition, we have established directly that the glucocorticoids amplify the glucagon stimulation of gluconeogenesis.

Characterization of cytochalasin B binding to adult rat liver parenchymal cells in primary culture

The characterization of cytochalasin B binding and the resulting effect on hexose transport in rat liver parenchymal cells in primary culture were studied. The cells were isolated from adult rats by perfusing the liver in situ with collagenase and separating the hepatocytes from the other cell types by differential centrifugation. The cells were established in primary culture on collagen-coated dishes. The binding of [4- 3H]cytochalasin B and transport of 3-O- methyl- D-[ 14 C]glucose into cells were investigated in monolayer culture followed by digestion of cells and scintillation counting of radioactivity. The binding of cytochalasin B to cells was rapid and reversible with association and dissociation being essentially complete within 2 min. Analysis of the kinetics of cytochalasin B binding by Scatchard plots revealed that binding was biphasic, with the parenchymal cell being extremely rich in high-affinity binding sites. The high-affinity site, thought to be the glucose-transport carrier, exhibited a K D of 2.86 · 10 −7 M, while the low-affinity site had a K D of 1.13 · 10 −5M. Sugar transport was monitored by 3-O- methyl- D- glucose uptake and it was found that cytochalasin B (10 −5M) drastically inhibited transport. However, D-glucose (10 −5M) did not displace cytochalasin B, and cytochalasin E, which does not inhibit transport, was competitive for cytochalasin B at only the low-affinity site, demonstrating that the cytochalasin B inhibition of sugar transport occurs at the high-affinity site but that the inhibition is non-competitive in nature. Therefore, the liver parenchymal cells may represent an unusually rich source of glucose-transport system which may be useful in the isolation of this important membrane carrier.

Interaction of epidermal growth factor with adult rat liver parenchymal cells in primary culture

Adult rat liver parenchymal cells in primary culture exhibit specific saturable binding of 125I-labeled murine epidermal growth factor (EGF). The Scatchard plot of the binding data obtained at 36 °C was curvilinear yielding two apparent dissociation constants of 1.5 × 10 −10 m and 1.2 × 10 −9 m with 27,000 and 57,000 sites per cell, respectively. The binding data obtained at 2 °C yielded a linear Scatchard plot with an apparent dissociation constant of 4.4 × 10 −9 m and 78,000 sites per cell. Exposure of the hepatocytes to EGF at 36 °C resulted in a loss of EGF binding capacity due to down regulation of receptors. The cells recovered the capacity to bind EGF upon incubation in medium which did not contain EGF; this recovery was inhibited by cycloheximide. The cultures appeared to internalize and degrade bound EGF at 36 °C but not at 2 °C. The degradation of EGF was inhibited by chloroquine, an inhibitor of lysosomal enzymes. These data indicate that liver specifically binds and further processes EGF, and therefore, may be a physiological target tissue for this growth factor.

Regulation of coenzyme A biosynthesis by glucagon and glucocorticoid in adult rat liver parenchymal cells.

We studied the effects of glucagon, dibutyryl cyclic AMP and dexamethasone on the rate of [(14)C]pantothenate conversion to CoA in adult rat liver parenchymal cells in primary culture. The presence of 30nm-glucagon increased the rate by about 1.5-fold relative to control cultures (range 1.4-2.3) and 2.4-fold relative to cultures containing 1-3m-i.u. of insulin/ml. The half-maximal effect was obtained at 3nm-glucagon. Dibutyryl cyclic AMP plus theophylline also enhanced the rate by about 1.5-fold. Dexamethasone acted synergistically with glucagon; glucagon at 0.3nm had no effect when added alone, but resulted in a 1.7-fold enhancement when added in the presence of dexamethasone (maximum effect at 50nm). The 1.4-fold enhancement caused by the addition of saturating glucagon concentrations was increased to a 3-fold overall enhancement by the addition of dexamethasone. However, dexamethasone added alone over the range 5nm to 5mum had no effect on the rate of [(14)C]pantothenate conversion to CoA. The stimulatory effect of dibutyryl cyclic AMP plus theophylline was also enhanced by the addition of dexamethasone. Changes in intracellular pantothenate concentration or radioactivity could not account for the stimulatory effects of glucagon, dibutyryl cyclic AMP or dexamethasone. Addition of 18mum-cycloheximide, an inhibitor of protein synthesis, decreased the rate of incorporation of [(14)C]pantothenate into CoA and the enhancement of this rate by glucagon and dibutyryl cyclic AMP plus theophylline in a reversible manner. These results demonstrate an influence of glucagon, dibutyryl cyclic AMP and glucocorticoids on the intracellular mechanism regulating total CoA concentrations in the liver.

Secretion of haem by hepatic parenchymal cells.

Hepatic parenchymal cells in primary culture, and also the intact perfused liver, secrete newly synthesized haem into extracellular fluids. In cultures incubated with the haem precursor delta-amino[4-14C]laevulinate, labelled haem was formed at a linear rate for at least 8 h, and 10-20% of the total labelled haem was present in the culture medium. The appearance of labelled extracellular haem was proportional both to the concentration of labelled precursor offered to the cells and to the time of incubation. Similar results were obtained when [2-14C]glycine was added as haem precursor. Studies with the isolated perfused liver indicated that newly synthesized haem is secreted also by the intact liver. Approximately equal amounts of haem appeared in the bile and in perfusate. The findings are discussed in relation to the pathogenesis of symptoms in the hereditary hepatic porphyrias.

Collagen production by rat liver parenchymal cells in primary culture.

Rat liver parenchymal and non-parenchymal cells were isolated by the collagenase perfusion method followed by Percoll density gradient centrifugation. The isolated parenchymal cells, when cultured for a few days, formed cords of polygonal cells which are typical for hepatocytes and produced a low (about 0.2% of total protein synthesized) but significant amount of collagen. This is the first demonstration of collagen production by hepatic parenchyma) cells in primary culture.

Adult liver parenchymal cells in primary culture: Characteristics and cell recognition standards

Primary cultures provide one method for studying liver biochemistry in vitro. The short term incubations of isolated cells employ homogenous cell populations, incubated in completely defined media. These cells are capable of exhibiting several of the in vivo functions. The long term cultures derived from adult liver parenchymal cells offer different advantages. For example, these cells can be cloned, isolated, injected into animals, and induced to synthesize increased amounts of some cell-specific enzymes. Organ cultures of adult liver are yet another in vitro system yielding important information on liver function.

Observations concerning the production and excretion of cholesterol in mammals. XII. Demonstration of the essential role of hepatic reticulo-endothelial cell (Kupffer cell) in the normal disposition of exogenously derived cholesterol.

ArticleObservations Concerning the Production and Excretion of Cholesterol in MammalsXII. Demonstration of the Essential Role of the Hepatic Reticulo-Endothelial Cell (Kupffer Cell) in the Normal Disposition of Exogenously Derived CholesterolMeyer Friedman, Sanford O. Byers, and Ray H. RosenmanMeyer FriedmanFrom the Harold Brunn Institute, Mount Zion Hospital, San Francisco, California, Sanford O. ByersFrom the Harold Brunn Institute, Mount Zion Hospital, San Francisco, California, and Ray H. RosenmanFrom the Harold Brunn Institute, Mount Zion Hospital, San Francisco, CaliforniaPublished Online:31 Mar 1954https://doi.org/10.1152/ajplegacy.1954.177.1.77MoreSectionsPDF (2 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByInteraction of the Reticuloendothelial System with Blood Lipid and Lipoprotein MetabolismRelative contributions of parenchymal and non-parenchymal (sinusoidal) liver cells in the uptake of chylomicron remnantsMetabolism, Vol. 30, No. 8Glycosaminoglycans and lipoprotein metabolism: An overviewPharmacological Research Communications, Vol. 11, No. 7Adult liver parenchymal cells in primary culture: Characteristics and cell recognition standardsIn Vitro, Vol. 10, No. 1-2Effects of oestrone and 2-methoxymethyl-17α-methyl-oestradiol-3-methyl ether (P-5780) on cholesterol metabolism in normo- and hypercholesterolaemic ratsJournal of Atherosclerosis Research, Vol. 8, No. 3Importance of Aging in the Relationships Between the Reticuloendothelial System and Cholesterol TransportArteriopathy Induced By Reticuloendothelial BlockadeBiochemistry of TriglyceridesLipid Metabolism by Macrophages and Its Relationship to AtherosclerosisAortic distribution and binding of C14-labeled cholesterol and lipomul by native rat aortas and aldehyde-crosslinked bovine aortasJournal of Surgical Research, Vol. 5, No. 9The Physiopathology of the Reticuloendothelial Cells of the liver and SpleenThe macrophage system, lipid metabolism and atherosclerosisJournal of Atherosclerosis Research, Vol. 4, No. 2FUNCTIONS OF THE KUPFFER CELLSSteroids and Lipid MetabolismAction of India ink and triton on the post-heparinic clearing factor releaseJournal of Atherosclerosis Research, Vol. 4, No. 1Phagocytosis with Special Reference to Hepatic Function and DiseaseMedical Clinics of North America, Vol. 47, No. 3Production of Arterial Lesions by a Humoral Factor in Parabiotic RatsCirculation Research, Vol. 12, No. 3Agents affecting lipid metabolism-I. on the inhibition of cholesterol biosynthesis by estrogensBiochemical Pharmacology, Vol. 11, No. 8The uptake and metabolism of C14-labeled fatty acids by macrophages in vitroJournal of Lipid Research, Vol. 3, No. 3Morphologische Befunde nach parenteraler Zufuhr feintropfiger FettemulsionenZeitschrift für Die Gesamte Experimentelle Medizin, Vol. 135, No. 6Cholesterol metabolism: A guide toward its understandingProgress in Cardiovascular Diseases, Vol. 4, No. 5Lactose Diets and Cholesterol MetabolismThe Journal of Nutrition, Vol. 76, No. 1Studies on the Characterization of Human Serum Lipoproteins Separated by Ultracentrifugation in a Density GradientThe American Journal of Clinical Nutrition, Vol. 9, No. 1Hormones, Cholesterol, and Coronary AtherosclerosisCirculation, Vol. 22, No. 3The Removal of Artificial Fat Emulsions from the Blood Stream of DogsActa Physiologica Scandinavica, Vol. 48, No. 3-4LIPIDS AND THE RETICULOENDOTHELIAL SYSTEM15 December 2006 | Annals of the New York Academy of Sciences, Vol. 88, No. 1The Effect of Low-Protein Diets Upon Serum Cholesterol in ManThe American Journal of Clinical Nutrition, Vol. 6, No. 3THE ROLE OF LYMPH CHOLESTEROL IN THE REGULATION OF ENDOGENOUS CHOLESTEROL AND CHOLESTEROL ESTER SYNTHESISJournal of Biological Chemistry, Vol. 230, No. 2Studies on Exogenous Cholesterol Metabolism in Human Atherosclerosis with the Aid of IsotopesObservations Concerning the Production and Excretion of Cholesterol in MammalsCirculation, Vol. 10, No. 4Mass Separation of Reticuloendothelial and Parenchymal Cells of Rat's LiverScience, Vol. 120, No. 3116 More from this issue > Volume 177Issue 1March 1954Pages 77-83 Copyright & PermissionsCopyright © 1954 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1954.177.1.77PubMed13148346History Received 7 October 1953 Published online 31 March 1954 Published in print 31 March 1954 Metrics