Rat Intestinal Lymph Research Articles

Identification and characterization of cow's milk proteins from the rat intestinal lymph using a proteomic strategy

Food proteins were considered to be absorbed into the body after being digested to amino acids, dipeptides, and tripeptides. However, there are studies indicating that some proteins can pass through the intestinal epithelium under normal physiological conditions, perhaps not in sufficient quantities to be of nutritional importance, but in quantities that may be antigenically or biologically active. In the present study, rat intestinal lymph samples were collected using a modified lymph fistula rat model in fasting and cow's milk postprandial states. Low molecular weight proteins were enriched by ultrafiltration and differential solubilization, separated by 1D-SDS-PAGE, digested in-gel based on molecular weight, and identified using nano-LC-MS/MS. In the postprandial rat intestinal lymph, nine bovine-specific proteins (false discovery rate ≤1%) were identified in different molecular weight regions. Most proteins identified in lymph were highly abundant proteins in the milk, such as β-lactoglobulin and caseins. Seven of the nine identified bovine-specific proteins are allergens in milk. This strategy can be used to search for proteins that can enter the intestinal lymph and analyze their common features. Understanding the common features of these proteins might help to develop protein drugs taken orally, so that therapeutic proteins might embody fusion domains for cross-barrier transport or translocation.

M1724 Effect of Different Kind of Dietary Lipid on Glucagon-Like Peptide-2 (GLP-2) Concentration in Intestinal Lymph of Rats

M1724 Effect of Different Kind of Dietary Lipid on Glucagon-Like Peptide-2 (GLP-2) Concentration in Intestinal Lymph of Rats

Intestinal Dendritic Cell Subsets: Differential Effects of Systemic TLR4 Stimulation on Migratory Fate and Activation In Vivo

Dendritic cells (DC) present peripheral Ags to T cells in lymph nodes, but also influence their differentiation (tolerance/immunity, Th1/Th2). To investigate how peripheral conditions affect DC properties and might subsequently regulate T cell differentiation, we examined the effects of a potent DC-activating, TLR-4-mediated stimulus, LPS, on rat intestinal and hepatic DC in vivo. Steady-state rat intestinal and hepatic lymph DC are alpha(E2) integrin(high) (CD103) and include two subsets, signal regulatory protein alpha (SIRPalpha)(hi/low), probably representing murine CD8alphaalpha(-/+) DC. Steady-state lamina propria DC are immature; surface MHC class II(low), but steady-state lymph DC are semimature, MHC class II(high), but CD80/86(low). Intravenous LPS induced rapid lamina propria DC emigration and increased lymph DC traffic without altering SIRPalpha(high)/SIRPalpha(low) proportions. CD80/86 expression on lymph or mesenteric node DC was not up-regulated after i.v. LPS. In contrast, i.v. LPS stimulated marked CD80/86 up-regulation on splenic DC. CD80/86 expression on intestinal lymph DC, however, was increased after in vitro culture with TNF-alpha or GM-CSF, but not with up to 5 mug/ml LPS. Steady-state SIRPalpha(low) DC localized to T cell areas of mesenteric nodes, spleen, and Peyer's patch, whereas SIRPalpha(high) DC were excluded from these areas. Intravenous LPS stimulated rapid and abundant SIRPalpha(high) DC accumulation in T cell areas of mesenteric nodes and spleen. In striking contrast, i.v. LPS had no effect on DC numbers or distribution in Peyer's patches. Our results suggest that any explanation of switching between tolerance and immunity as well as involving changes in DC activation status must also take into account differential migration of DC subsets.

Intravital Demonstration of Modulation of T Lymphocyte Migration by CINC/gro in Rat Peyer’s Patches

Background/Aims: Cytokine-induced neutrophil chemoattractant (CINC/gro), a member of interleukin-8 family, was found as a potent chemotactic factor for rat neutrophils. Although several chemokines have been shown to be potent regulators of T cell chemotaxis in vitro, the potential role of chemokines in T-cell migration in gut-associated lymphoid tissues has not been investigated in vivo. In the present study, the effects of CINC/gro on T-lymphocyte migration were examined in rat Peyer’s patches. Methods: T lymphocytes collected from intestinal lymph of rats were fluorescence-labeled and injected into the jugular vein. Peyer’s patches of the recipient rats were observed with intravital fluorescence microscopy and the effects of CINC/gro infusion was investigated. Lymphocyte flux in mesenteric collecting lymphatics was also observed. Results: In vivo infusion of CINC/gro significantly attenuated the initial lymphocyte interaction with postcapillary venules of Peyer’s patches. However, once these lymphocytes adhered to venules, CINC/gro treatment significantly accelerated the transendothelial migration of T lymphocytes and they also significantly increased their subsequent flux in collecting lymphatics. Conclusion: There is a possibility that CINC/gro could modulate the characteristics of T lymphocyte homing in the inflammatory sites of gut.

A discrete subpopulation of dendritic cells transports apoptotic intestinal epithelial cells to T cell areas of mesenteric lymph nodes.

This study identifies a dendritic cell (DC) subset that constitutively transports apoptotic intestinal epithelial cell remnants to T cell areas of mesenteric lymph nodes in vivo. Rat intestinal lymph contains two DC populations. Both populations have typical DC morphology, are major histocompatibility complex class II(hi), and express OX62, CD11c, and B7. CD4(+)/OX41(+) DCs are strong antigen-presenting cells (APCs). CD4(-)/OX41(-) DCs are weak APCs and contain cytoplasmic apoptotic DNA, epithelial cell-restricted cytokeratins, and nonspecific esterase (NSE)(+) inclusions, not seen in OX41(+) DCs. Identical patterns of NSE electrophoretic variants exist in CD4(-)/OX41(-) DCs, intestinal epithelial cells, and mesenteric node DCs but not in other DC populations, macrophages, or tissues. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL)-positive DCs and strongly NSE(+) DCs are present in intestinal lamina propria. Peyer's patches and mesenteric but not other lymph nodes contain many strongly NSE(+) DCs in interfollicular and T cell areas. Similar DCs are seen in the ileum and in T cell areas of mesenteric nodes in gnotobiotic rats. These results show that a distinct DC subset constitutively endocytoses and transports apoptotic cells to T cell areas and suggest a role for these DCs in inducing and maintaining peripheral self-tolerance.

Altered migration of gut-derived T lymphocytes after activation with concanavalin A.

Although activation of lymphocytes is known to be associated with profound changes in homing behavior, it remains unclear how activation alters migration of gut-derived lymphocytes in lymphoid and nonlymphoid organs. The objectives of this study were 1) to compare migration of naive and concanavalin A (ConA)-activated T lymphocytes into the gut mucosa, spleen, and liver and 2) to define the role of specific adhesion molecules in this homing process. Fluorescently labeled T lymphocytes collected from rat intestinal lymph were injected into the jugular vein, and the kinetics of appearance of the infused lymphocytes were monitored in ileal Peyer's patches, spleen, and liver. The migration of naive and ConA-activated T lymphocytes into microvessels were compared using an intravital microscope. ConA stimulation significantly increased the rolling velocity of T lymphocytes in postcapillary venules of Peyer's patches, and ConA-stimulated lymphocytes exhibited a loss of the selective adherence properties in Peyer's patches that is normally observed with naive T cells. ConA activation also suppressed the accumulation of T cells in the spleen. On the other hand, the adherence of T cells to hepatic sinusoidal endothelium was significantly increased after ConA activation, especially in the periportal area, and this increase was attenuated by an anti-intercellular adhesion molecule (ICAM)-1 antibody. Flow cytometry analysis revealed a decline in L-selectin expression and an increase in CD11a expression and ICAM-1 on the surface of ConA-treated T cells. In conclusion, activation of gut-derived T lymphocytes with ConA significantly alters their migration path, with a diminished localization to Peyer's patches and spleen and a preferential accumulation in hepatic sinusoids. This altered migration pattern likely results from changes in the expression of leukocyte adhesion molecules such as L-selectin and CD11a.

Nitric oxide modulates T-lymphocyte migration in Peyer's patches and villous submucosa of rat small intestine

Background & Aims: Although nitric oxide (NO) is known to influence the recruitment of neutrophils in inflamed tissue, its role in lymphocyte-endothelial cell interactions remains poorly understood. The objectives of this study were to assess the effects of NO synthesis inhibition on T-lymphocyte migration in microvessels of rat small intestine and to define the role of adhesion molecules in this process. Methods: T lymphocytes collected from rat intestinal lymph were labeled with carboxyfluorescein diacetate succinimidyl ester and injected into the jugular vein of recipient rats. The migration of T lymphocytes into normal and N G -nitro- L-arginine methyl ester ( L-NAME)-treated intestinal microvessels was monitored by using an intravital microscope. Results: L-NAME significantly increased rolling and adherence of lymphocytes in postcapillary venules of Peyer's patches and submucosal venules without significantly decreasing red blood cell velocity. The subsequent appearance of lymphocytes in the initial lymphatics was also accelerated by L-NAME. Anti–α4-integrin antibody markedly inhibited the L-NAME–induced lymphocyte-endothelial cell interaction. Anti–P-selectin monoclonal antibody also significantly attenuated these adhesive interactions in both vascular regions. Conclusions: These data suggest that NO is an important modulator of lymphocyte migration in Peyer's patches and in nonlymphoid regions of the intestine. GASTROENTEROLOGY 1998;115:618-627

Dendritic Cell Heterogeneity In Vivo: Two Functionally Different Dendritic Cell Populations in Rat Intestinal Lymph Can Be Distinguished by CD4 Expression

DC derived from rat pseudo-afferent lymph (L-DC) vary in CD4, CD11b/c, Thy1, and OX41 expression. CD4 and OX41 are expressed by the same subpopulation (50-60%) of L-DC. CD4+/OX41+ L-DC express short fine processes and low nonspecific esterase, whereas CD4- DC/OX41- express long pseudopodia, high nonspecific esterase, and many cytoplasmic inclusions. These differences are stable in culture. Both populations express similar amounts of MHC class II, ICAM-1, CD11b/c and OX62. Most CD4-/OX41- L-DC are strongly positive for B7, but CD4+ L-DC express less B7, and some may be negative. Both populations express invariant chain, but both the absolute numbers and levels of expression were higher for CD4- DC. Surprisingly, CD4+ L-DC are more potent APC than CD4- cells in MLRs, for sensitized T cells in vitro and for naive T cells in vivo. Cultured CD4+/OX41+ DC can still process and present native Ag. Cultured CD4-/OX41- cells cannot present native Ag but can stimulate strong MLRs. CD4- DC invariant chain expression decreases in culture, whereas expression by CD4+ DC is stable for 48 h. CD4+ and CD4- L-DC have similar turnover times in vivo, suggesting that one population is not the precursor of the other. Thus, two separate DC populations that differ functionally and phenotypically migrate from intestine to mesenteric nodes. This may reflect distinct DC lineages or differentiation modulated by different microenvironmental stimuli.

Enhanced lymphocyte interaction in postcapillary venules of Peyer's patches during fat absorption in rats

BACKGROUND & AIMS: Although dietary fat is known to modulate immune functions, there is a paucity of data concerning the effects of fat absorption on migration of lymphocytes in intestinal lymphoid tissue. The objective of this study was to assess the influence of fat absorption on T-lymphocyte migration in Peyer's patches.METHODS: T lymphocytes collected from rat intestinal lymph were labeled with carboxyfluorescein diacetate succinimidyl ester and injected into the jugular vein of recipient rats. Olive oil or octanoic acid was placed into the duodenum, and Peyer's patch microcirculation was observed by intravital fluorescence microscopy.RESULTS: Rolling and adherence of lymphocytes in postcapillary venules were noted in both fasted and fed rats. However, lymphocyte adherence was significantly greater in olive oil-fed rats than in fasted rats. Olive oil also significantly increased the transendothelial migration of T lymphocytes. Octanoic acid stimulated lymphocyte rolling but did not affect lymphocyte adherence. Olive oil enhanced the expression of both alpha4-integrin and L-selectin on lymphocytes, whereas octanoic acid only increased the expression of L-selectin.CONCLUSIONS: Lymphocyte rolling and adherence are enhanced by olive oil feeding, possibly through an interaction between activated adhesion molecules on lymphocytes and counter- receptors on endothelial cells.(Gastroenterology 1997 Mar;112(3):813-25)

Vasoactive intestinal peptide modulates T lymphocyte migration in Peyer's patches of rat small intestine.

Although vasoactive intestinal peptide (VIP) has been postulated to function in modulation of T cell trafficking, the exact mechanism has not been elucidated in vivo. In the present study, the effects of VIP on T lymphocyte migration were examined in rat Peyer's patches. T lymphocytes collected from intestinal lymph of rats were labeled with carboxyfluorescein diacetate succinimidyl ester and injected into the jugular vein. Peyer's patches of the recipient rats were observed with intravital fluorescence microscopy. In vivo intra-arterial infusion of or in vitro incubation with VIP did not affect the initial lymphocyte interaction with postcapillary venules of Peyer's patches. However, these treatments with VIP significantly inhibited transendothelial migration and also significantly blocked the interstitial migration of T cells and inhibited their subsequent appearance in the interfollicular lymphatics. Treatment with adenosine 3',5'-cyclic monophosphate (cAMP)-inducing agents resulted in similar inhibitory effect on T lymphocyte migration in Peyer's patches. In conclusion, VIP has significant inhibitory effects on T lymphocyte migration in Peyer's patches, possibly mediated by elevation of the intracellular cAMP concentrations.

肝細胞とリポ蛋白の相互関係

In this study we investigated the effect of chylomicron or its remnant on intracellular metabolism of apoproteins with use of HepG2 cells.Following incubation for 24hrs at 37°C with chylomicron or its remnant obtained from rat intestinal lymph (40μg/ml cholesterol), cells were washed three times with the same medium and incubated for 12 hours in 1ml of the same medium to which 100μCi L-[35S]methionine was added. Newly synthesized apo E and B were precipitated by the specific antiserum, and were displayed by SDS-PAGE. Processing of fluorography was performed by using En3Hance. The gels were then exposed to X-ray film.Incubation of chylomicron with HepG2 resulted in increase in apo E accumulation in the medium after 12h incubation with 35S-methionine. However, apo E mRNA was not increased in the cells incubated with chylomicron or its remnant (test cells), suggesting that there is no increase in apo E synthesis. The fluorography of SDS-PAGE and two dimensional electrophoresis revealed that the apo E secreted from the test cells was larger in molecular weight and slightly acidic. Neuraminidase treatment of apo E from the test cells, however, resulted in two distinct bands of apo E, while that of apo E from control cells result in only one band of apo E, suggesting that the change in molecular weight and charge is not due to modification with sialic acid. The test cells secreted apo E lineally up to 24h after incubation with 35S-methionine, while the control cells secreted apo E lineally up to 6h and then accumulation of apo E in the medium reached to plateau, suggesting that apo E from test cells was not taken up by the cells. Presumably, this abnormal apo E is not taken up by the liver just after secretion, but reaches to the vascular wall cells.

Alkaline phosphatase of rat intestinal lymph: Its characterization and the effect of fat administration

Biological characteristics of alkaline phosphatase (ALP) from rat intestine were compared among four various fractions (brush border, cytosol, luminal and lymph) to clarify the source and route of ALP appeared in intestinal lymphatics. ALP of each fraction had the same K m values and the same heat stability and all were of intestinal type. However, lymph and cytosol ALP showed similar affinity to three kinds of lectins and were distinct from membrane and luminal ALP. On polyacrylamide gel electrophoresis (PAGE), there seems to be two types of charge isomers of intestinal ALP, namely brush border type and lymph type. On sodium dodecyl sulfate (SDS)-PAGE, the molecular weight of principal band for each form was: 130,000 for brush border type, and 160,000 for lymph type. Fat administration significantly increased the ALP activity in intestinal lumen and intestinal lymph. However, it did not change biological characteristics of ALP including binding ability to lectins and electrophoretic mobility in any of these four fractions. These results suggest that lymphatic ALP may be transported from cytosol of intestinal cells and that fat administration seems to induce quantitative change of intestinal ALP, but not to change its physiological route of transportation into intestinal lymph.

Rat intestinal lymph osmolarity during glucose and oleic acid absorption.

The two major purposes of this study were to determine 1) how glucose and oleic acid absorption by the intestinal villi influenced the osmotic composition of lymph as it exited the villus base and 2) what if any changes in lymph osmolarity occurred as the lymph traversed through the bowel wall. The rat jejunum was used in all studies and lymph was collected from individual lymphatics at 0.5-1 nl/min during control states and luminal exposure to 35-550 mg% glucose solutions (isotonic in saline) and 5 and 20 mM oleic acidtaurocholate solutions. Lymph collected from the base of villi during vigorous motility had an osmolarity of 403 +/- 15 mosM at rest and was only increased 30-50 mosM more except during exposure to 550 mg% glucose, where osmolarity increased over 100 mosM. Under comparable conditions, the submucosal lymph osmolarity at rest was 302 +/- 3.5 mosM and increased to 330-350 mosM during exposure to all of the solutions tested. When intestinal motility was virtually stopped, the submucosal lymph osmolarity was isotonic for all solutions tested. These observations indicate that absorption of glucose and oleic acid increased the osmolarity of lymph, leaving the villus only 30-50 mosM unless a glucose concentration of 550 mg% was present. Furthermore, the increased flow of villus lymph during absorption raised the osmolarity of the submucosal lymph when bowel motility assisted the lymph propulsion. This movement of materials from the villus to the submucosa by venular blood and lymph flow provides an opportunity for the villus tissue to influence the composition of the submucosal interstitial environment.

Effect of dietary and infused lactose on rat intestinal lymph lipids.

Twenty-four male, 6- to 8-week-old Sprague-Dawley rats were fed one of two skim-milk-based diets or stock laboratory diet for 100-120 days to assess the effect of dietary and infused lactose on intestinal lymph lipids. One skim-milk-based diet had its lactose enzymatically hydrolyzed by commercial beta-galactosidase to its constituent monosaccharides galactose and glucose, while the second skim milk diet was unaltered. Serum triglycerides, but not serum cholesterol, were higher in the lactose- versus the glucose-/galactose-adapted rats at 90 days. There was no diet-associated qualitative difference in serum lipoproteins as analyzed by agarose gel electrophoresis. After the rats had consumed the diets for 100-120 days, 0.9% saline and 20% solutions of lactose, and equimolar mixtures of glucose/galactose, glucose and maltose were infused sequentially via a duodenal cannula, then intestinal lymph was collected via a mesenteric lymph duct cannula, the only significant difference was a 134% increase in lymph cholesterol, but not lymph triglyceride output, when lactose was infused into lactose-adapted rats.

ChemInform Abstract: A Lymphotropic Prodrug of L‐Dopa: Synthesis, Pharmacological Properties and Pharmacokinetic Behavior of 1,3‐Dihexadecanoyl‐2‐[(S)‐2‐amino‐3‐ (3,4‐dihydroxyphenyl)propanoyl]propane‐1,2,3‐triol.

AbstractDer ausgehend von geschütztem L‐Dopa (I) hergestellte Ester (III) zeigt anti‐Parkinson‐Aktivität (längere Wirkungsdauer als L‐Dopa).

Lymph pressure in rat intestinal lymph duct with lymphatic obstruction.

Lymph pressure (PL) in the main intestinal lymph duct with obstruction of lymph flow was determined. Under various conditions, the rate of lymph flow (JL) was essentially the same in either A rats (with communications between hepatic and intestinal lymphatics) or B rats (without such communications), but PL of A rats was significantly lower (P less than 0.01) than that of B rats. When the intestine was in the basal state, JL of A and B rats was 0.2-0.3 ml/h per rat, and PL was 1.5 +/- 0.2 and 3.3 +/- 0.2 mm/Hg, respectively. During fluid absorption, JL of A and B rats increased to 0.8-0.9 ml/h, and PL was 2.1 +/- 0.4 and 6.4 +/- 0.7 mmHg, respectively. During intravenous saline infusion, JL of A and B rats increased greatly to approximately 14 ml/h, and PL was 3.1 +/- 0.3 and 10.4 +/- 1.1 mmHg, respectively. The lower PL in A rats is apparently due to the possibility that during lymphatic obstruction most lymph could be drained off by the hepatic lymphatics. In A rats, luminal distension pressure had no effect on PL but in B rats PL decreased when distension pressure was 20 mmHg or higher. Furthermore, lymph pressure waves indicate the occurrence of rhythmical contractions of the lymph duct or its surrounding tissues, which may play a role in the propulsion of lymph.

A lymphotropic prodrug of L-dopa: synthesis, pharmacological properties, and pharmacokinetic behavior of 1,3-dihexadecanoyl-2-[(S)-2-amino-3-(3,4-dihydroxyphenyl)prop anoyl] propane-1,2,3-triol.

A glyceride derivative of L-Dopa, 1,3-dihexadecanoyl-2-[(S)-2-amino-3-(3,4-dihydroxyphenyl)propan oyl] propane-1,2,3-triol (1), was synthesized and tested as an orally administrable prodrug endowed with lymphotropic properties. In the oxotremorine and reserpine tests, 1 exhibited an anti-Parkinsonian activity of longer duration than L-Dopa. The time course of concentration of 1 in the intestinal lymph of rat was determined and compared to that of L-Dopa. The results clearly demonstrate that 1 is selectively absorbed from the intestinal tract by the lymphatic route without any chemical or enzymatic degradation. In the blood of rats and mice, 1 functions as a prodrug to release L-Dopa by hydrolysis. In comparison with L-Dopa itself, higher L-Dopa levels for a longer period of time were observed as well as much more favorable L-Dopa/dopamine ratios. Ultimately, studies using mice show that the administration of 1 brings about a prolonged increase of L-Dopa and dopamine levels in the brain, without initial transient peak in concentration observed after an equimolecular dose of L-Dopa.

Metabolism of protein-free lipid emulsion models of chylomicrons in rats.

Emulsions were prepared by ultrasonication of mixtures of triolein, cholesteryl oleate, phosphatidylcholine and cholesterol in aqueous dispersions, then purified by ultracentrifugation. After injection into rats, the metabolism of the artificial, protein-free emulsions was comparable to the metabolism of chylomicrons collected from rat intestinal lymph during the absorption of fat. Like chylomicrons, the emulsion triacylglycerol was removed from the plasma more quickly than emulsion cholesteryl ester. Also like chylomicrons, much more emulsion cholesteryl ester than triacylglycerol appeared in the liver 10 min after injection, and only trace amounts appeared in the spleen. Because the artificial emulsions gained apolipoproteins when incubated with plasma, their metabolism was probably facilitated by the recipient rat plasma apolipoproteins and so, in rats made apolipoprotein-deficient by treatment with estrogen, the removal of emulsions from the plasma was slowed. Removal was also slowed in hyperlipidemic rats fed a high-fat, high-cholesterol diet to expand the plasma pools of the triacylglycerol-rich lipoproteins and remnants. The results indicate that the metabolism of lymph chylomicrons can be modeled by artificial, protein-free lipid emulsions not only in the initial partial hydrolysis by lipoprotein lipase, but also in the delivery of a remnant-like particle to the liver.

Receptors for homologous plasma lipoproteins on a rat hepatoma cell line.

Hepatocytes express on their surfaces more than one class of receptors capable of mediating the internalization of lipoproteins. However, relatively little is known about the binding characteristics of hepatic receptors for various lipoproteins, about the regulation of the receptors, and about the consequences for intracellular lipid metabolism of uptake of lipoproteins via different classes of receptors. The aim of the present studies was to characterize the binding and degradation of various lipoproteins and their mutual competition for cellular processing. Since these kinds of studies may be more easily carried out in continuous established hepatoma cell lines than in nondividing primary hepatocyte cultures, we examined the lipoprotein receptor functions of a well differentiated rat hepatoma (H-35). Cells were grown to confluence in Eagle's minimal essential medium in 15% newborn calf serum. Medium then was changed to 15% lipoprotein-deficient serum for 44 hr before experiments. External binding of 125I-labeled rat plasma and intestinal lymph lipoproteins was assessed at 4 degrees C. Cellular uptake and degradation were assessed at 37 degrees C. Lipoproteins were isolated by fixed angle or zonal ultracentrifugation or by heparin affinity column chromatography and characterized as to their lipid and apoprotein compositions. Labeled low density (LDL), high density (HDL2), non-apoE-HDL, very low density lipoproteins (VLDL), and chylomicron remnants (CM-R) each manifested specific and saturable binding and degradation by the hepatoma cells. Competition experiments indicated that separate receptors were present for LDL, HDL2, and CM-R. Most of HDL2 appeared to be bound to the non-apoE-HDL receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

In vivo uptake of chylomicron [3H]retinyl ester by rat liver: evidence for retinol transfer from parenchymal to nonparenchymal cells.

We have studied hepatic uptake of chylomicron retinyl ester. Chylomicrons were obtained from intestinal lymph of rats that were given retinol in groundnut oil by intraduodenal injection. When lymph was injected intravenously into normal rats, the radioactivity was cleared from blood with t1/2 approximately equal to 10 min. Retinyl ester was taken up initially by the liver, which, after 30 min, contained 80-90% of the radioactivity injected. Initially, most of the radioactivity was in hepatocytes, but after 30 min it disappeared from these cells and reappeared in nonparenchymal liver cells. After 2 hr these cells contained more radioactivity than the hepatocytes. When lymph was injected into vitamin A-deficient rats or rats given vitamin A in the form of retinoic acid, the plasma clearance and initial hepatic uptake of radioactivity were similar to that found in control animals. However, the nonparenchymal cells in these animals did not accumulate radioactivity. The current data suggest that vitamin A (in chylomicron remnants) is taken up initially by hepatocytes and then is released from these cells and delivered mainly to nonparenchymal liver cells in normal animals. In vitamin A-deficient rats, the vitamin is transferred from the hepatocytes to extrahepatic tissues.