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Effect of irreversible dermal necrosis on phagocytic activity of reticuloendothelial system.

A model of full-thickness dermal necrosis was produced in rats by the application of liquid nitrogen to a 20% total body surface area of the dorsal skin surface. In this model there was an alteration of reticuloendothelial system phagocytic activity of the lung and spleen as measured by the uptake of technetium 99m-labeled sulfur colloid in vivo. The present results suggest that marked alterations in reticuloendothelial system phagocytic activity can be produced by full-thickness dermal necrosis in the absence of heat.

Animals↗

Chondroitin sulfate iron colloid as an MR contrast agent for the hepatic reticuloendothelial system.

OBJECTIVE: Chondroitin sulfate iron colloid (CSI), a therapeutic agent for asiderotic anemia, is widely used in the clinical field, and its safety has been established in Japan. We studied the potential of this agent for MRI of the hepatic reticuloendothelial system. Chondroitin sulfate iron colloid has a paramagnetic trivalent iron ion and is effective in shortening T2 relaxation time because it is taken up rapidly in the hepatic reticuloendothelial system after intravenous injection. MATERIALS AND METHODS: Hepatic MR images were obtained before and 1 h after the intravenous injection of 26.9 mumol Fe/kg of CSI in rats with experimentally induced tumors and of 18-30 mumol Fe/kg in human subjects. RESULTS: The signal intensities of normal hepatic tissue were decreased in all cases, whereas those of tumors were unchanged after CSI injection in these two series. Consequently, good contrast was observed in each pulse sequence. CONCLUSION: Therefore, CSI seems to be clinically useful as a contrast agent for hepatic MRI.

Animals↗

[Phagocytosis of the reticuloendothelial system in diabetes mellitus].

It has been assumed that patients with diabetes mellitus (DM), who are usually susceptible to bacterial infections, have a depression of the antibacterial defense mechanism. This study was undertaken to substantiate the hypothesis that phagocytosis of the reticuloendothelial system (RES) is depressed in diabetic patients. It is believed that intravenously injected colloidal suspensions whose particles are unable to pass through the capillary barrier will be phagocytized mainly by the reticuloendothelial cells in the liver and spleen. In the present study, the RES phagocytic index (RESPI) was measured in 48 subjects: 20 normal controls and 28 patients with DM. Measurements were based on the rate of disappearance (T1/2) of radioactivity in the heart (blood pooling) after rapid I.V. injection of 3mCi of Tc-99m phytate (2mg phytate). Using a gamma camera, sequential images of the liver and heart were obtained, and computer-generated time-activity curves were established. The T1/2 was then calculated. Our results revealed that the RESPI values in the DM group were significantly increased as compared to the normal control group (normal control = 4.60 +/- 1.01; DM = 6.78 +/- 3.83; P < 0.05). This prolonged half-disappearance time of blood radioactivity in diabetic patients is interpreted as a reflection of impaired phagocytotic efficiency in the reticuloendothelial system. The results of this preliminary study add support to the in vivo evidence explaining the increased susceptibility to infection in diabetic patients.

Adolescent↗

Iron overload in reticuloendothelial systems of pediatric oncology patients who have undergone transfusions: MR observations.

OBJECTIVE: Pediatric oncology patients who undergo intensive chemotherapy develop anemia caused by myeloid suppression that necessitates transfusions that, in turn, cause iron deposition in the reticuloendothelial system. We describe MR imaging of iron overload in pediatric patients who underwent such chemotherapy and who have solid and hematologic tumors. MATERIALS AND METHODS: The MR appearance of the liver, spleen, and bone marrow was evaluated in 13 children with both solid (n = 10) and hematologic (n = 3) malignant lesions using known criteria for the presence of iron deposition. Findings were correlated with transfusional history, chemotherapeutic regimens, and ferritin levels. RESULTS: MR imaging obtained after chemotherapy and transfusional therapy revealed signs of iron deposition in the liver and spleen, particularly on T2-weighted images. Bone marrow signal intensity varied among patients. Pancreatic signal intensity was normal. Ferritin levels were elevated in all patients. CONCLUSION: Reticuloendothelial system iron deposition present in follow-up MR imaging of pediatric solid and hematologic malignant lesions reflected the intensity of the chemotherapeutic regimen, the degree of myeloid suppression, and the resultant transfusional requirements. Such iron deposition appeared to have no effect on cardiac, liver, or pancreatic function.

Adolescent↗

Reticuloendothelial system uptake of infused 125I-trypsin in newborn and adult rats.

Previous studies have demonstrated enhanced intestinal trypsin uptake and decreased liver clearance of trypsin in newborn rats compared to adults. In order to examine the effectiveness of the reticuloendothelial system (RES) in clearing trypsin, bovine trypsin (1.25 mg/100 g body weight) plus trace 125I-trypsin were injected into the portal vein of 2-week-old (n = 57) and adult (n = 44) control rats or following RES stimulation using intraperitoneally injected lipopolysaccharide or RES suppression with intraperitoneally injected oleic acid emulsion. Plasma, liver and spleen 125I activities were assessed at 1, 5 or 15 min following infusion in control, stimulated and suppressed animals. Newborn control rats had significantly increased 125I plasma levels with decreased liver and spleen 125I activity compared to control adults. RES stimulation in the newborns did not lead to any change in liver or plasma levels although splenic values increased while adults had a decrease in liver 125I activity. RES suppression in the newborns led to increased plasma and decreased spleen 125I-trypsin values while adult rat levels were unchanged. The immature reticuloendothelial system in newborns is poorly responsive to RES stimulation although it can be made even further inefficient by RES suppression. The combination of RES immaturity and lack of response to stimulation may make newborns susceptible to proteolytic damage, especially during times of increased systemic levels of proteolytic enzymes.

Aging↗

Enhancement of resistance to murine osteogenic sarcoma in vivo by an extract of Brucella abortus (Bru-Pel): association with activation of reticuloendothelial system macrophages.

The administration of an aqueous-ether extracted residue of Brucella abortus (Bru-Pel) inhibits development of transplanted osteogenic sarcomas in mice as evidenced by a decrease in mortality. At least one mechanism through which Bru-Pel modulates host resistance is activation of macrophages of the reticuloendothelial system. Peritoneal macrophages harvested from mice receiving Bru-Pel were cytotoxic for osteogenic sarcoma cells in vitro, limited the replication of vaccinia virus in cell cultures, and demonstrated enhanced emittance of chemiluminescence during phagocytosis of zymosan particles of Candida albicans. The concept of reticuloendothelial system activation was further supported by the evidence that administration of Bru-Pel enhanced resistance of mice to challenge with a lethal inoculum of Listeria monocytogenes. These observation support the hypothesis that Bru-Pel shares a number of characteristics with recognized immunomodulating agents and that one mechanism by which it modulates host resistance to tumors, to virus infections, and to challenge with L. monocytogenes is through activation of macrophages.

Animals↗

Defective reticuloendothelial system function in rheumatoid arthritis.

The function of the splenic reticuloendothelial system in patients with rheumatoid arthritis (R.A.) was assessed by determining the clearance of autologous heat-damaged erythrocytes from the circulation. 11/13 patients with active R.A. had a defect in the clearance of red cells and there was a significant inverse correlation between splenic function and the level of circulating immune complexes detected by a Clq-binding assay. Splenic function was normal in 13 patients with inactive disease who had been treated with either gold or prednisone. A serial study on 1 patient with active R.A. showed a clear correlation between fluctuations in disease activity, splenic function, and the level of circulating immune complexes.

Adult↗

Reticuloendothelial system function test using 131I-labeled aggregated albumin.

The reticuloendothelial system function test using 131I-labeled aggregated human albumin (131IAA) as test particle is thought to be one of the best methods for the study of RES function of human beings. This method needs a large amount of 131IAA, but 131IAA has been used as a tracer of liver scintiscanning, and we tired to study RES function by using commercially available 131IAA specially made as tracer of liver scintiscanning. Because the amount of 131IAA used in this study was smaller than the critical dosis, our interest was focussed on the catabolic activity of 131IAA phagocytized by Kupffer's cells. The plasma obtained 60 min after 131IAA injection was fractionated into two distinct peaks by gel column chromatography; ionic 131I and protein-bound 131IAA. The ratio between ionic 131I and bound 131IAA (F/B ratio) was studied in various diseases. The F/B ratios of liver cirrhosis and hepatoma were significantly lower than that of the control. The lowered F/B ratio had no correlation with other liver function tests, data of hepatic scintiscanning, or with clinical findings. The F/B ratio was also not correlated with congo red index as RES function test.

Adult↗

Quantitation of the reticuloendothelial system clearance of soluble fibrin.

Phagocytosis of particulate fibrin has been previously established as a function of the reticuloendothelial system (RES). More recently, reticuloendothelial cells have been shown to bind soluble fibrin/fibrinogen (f/F) complexes in vitro. To quantitate RES clearance vs microthrombus formation, varying doses (0.1-6 mg/kg) of 125I-soluble f/F was injected into rabbits. One hour later the animals were killed, at which time 48 +/- 8% of the 125I f/F had been cleared from the blood. Homogenized organ samples were separated into insoluble pellet, soluble protein bound, and free 125I. Treatment of other samples with plasmin prior to homogenization differentiated the insoluble 125I into RES cleared (intracellular-plasmin resistant) vs microthrombi (plasmin sensitive pellet 125I). 125I-f/F was chiefly found in liver and spleen. Injection of low f/F concentrations resulted in no plasmin sensitive pellet 125I. 3 mg/kg f/F caused small, variable amounts of plasmin sensitive pellet 125I, chiefly in the kidney. With 6 mg/kg, 21-50% of the insoluble 125I in all organs was plasmin sensitive, and occasional 1-2 mm thrombi were found. The data indicate complete and rapid RES clearance of small amounts of soluble f/F from the blood, without microthrombi being formed. The RES was acutely saturated at 1.5-3.0 mg f/F/kg, which is equivalent to immediate conversion to fibrin of 1-2% of the intravascular fibrinogen pool.

Animals↗

Reticuloendothelial system Fc receptor-mediated clearance of IgG-tagged erythrocytes from the circulation of patients with idiopathic ulcerative colitis and chronic liver disease.

Immune complexes may be important in the pathogenesis of the liver disease associated with idiopathic ulcerative colitis. In the present study, we documented Fc receptor-mediated clearance by the reticuloendothelial system of immune complex-like material from the systemic circulation of 25 healthy control subjects, 19 patients with ulcerative colitis alone, 9 patients with ulcerative colitis and elevated liver enzyme tests and 8 patients with various other forms of chronic liver disease. Following an intravenous infusion of IgG-tagged 51Cr-labeled autologous erythrocytes, serial blood samples were drawn over a 2-hr period of time, and computer-generated clearance curves were obtained. The time required for clearance of 50% of infused erythrocytes (T1/2) was then calculated. Serum immunoglobulin (IgA, IgG and IgM), complement (C3 and C4) and immune complex-like activity (IgG and IgM types) were also determined. Sixteen of 19 (84%) ulcerative colitis patients and 7 of 8 (88%) chronic liver disease patients had normal clearance T1/2's (when compared to 25 healthy controls). Conversely, only 1 of 9 (11%) ulcerative colitis + chronic liver disease patients demonstrated normal clearance function. Aside from serum IgM levels, the results of serum immunoglobulin, complement and immune complex-like determinations were similar in ulcerative colitis and ulcerative colitis + chronic liver disease patients. Serum IgM levels, however, were significantly decreased in ulcerative colitis patients and increased in ulcerative colitis + chronic liver disease patients (p less than 0.001). The results indicate that the reticuloendothelial system of patients with ulcerative colitis and chronic liver disease is impaired in its ability to dear immune complex-like material from the systemic circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Metastasis: reticuloendothelial system and organ retention of disseminated malignant cells.

The lung retention patterns of B16 melanoma cells were determined after intravenous injection of [125l]dUrd-labelled tumor cells into B16 melanomabearing mice. Experiments were performed with mice undergoing acute or chronic reactions to bacterial endotoxin or zymosan, both of which were shown to modify the activity of the reticuloendothelial system as assessed by carbon clearance assays. On the one hand, the release of arrested melanoma cells from the lungs was retarded in mice with both endotoxin-and zymosan- induced acute inflammation. There was a parallel increase in the numbers of pulmonary tumor nodules which developed after injection of non-radiolabelled melanoma cells into similarly treated groups of mice. On the other hand, fewer tumor cells were retained in the lungs of mice undergoing chronic responses to endotoxin, and fewer pulmonary tumor nodules subsequently arose after injection of unlabelled cells. However, in mice pre-treated with zymosan, retention of melanoma cells was not different from that in controls and greatly increased numbers of pulmonary nodules grew in zymosan pre-treated mice receiving non-radiolabelled cells. These experiments were discussed in terms of the contribution of the reticuloendothelial system to the release of arrested cancer cells from the pulmonary vasculature.

Animals↗

Metastasis and the reticuloendothelial system. II. Effect of triamcinolone acetonide on organ retention of malignant cells in endotoxin-treated mice.

The lung retention patterns of B16 melanoma cells were determined after intravenous injection of [125i]dUrd-labelled tumor cells into B16 melanoma-bearing mice. Experiments were performed to assess the effects of a synthetic glucocorticoid, triamcinolone acetonide, on the retention of B16 melanoma cell arrested in the lungs of mice with endotoxin-induced reticuloendothelial system hyperfunction. Lung clearance of malignant cells was greatly accelerated in mice treated with endotoxin alone but was markedly inhibited in mice with only triamcinolone acetonide. In mice treated with both endotoxin and subsequently triamcinolone acetonide after tumor-cell arrest processes had occurred, the endotoxin-induced increase in clearance was nullified. These results are discussed in terms of the mutually antagonistic activity of both pharmacologic agents upon the reticuloendothelial system and the role of the latter in regulating organ retention of disseminated malignant cells.

Animals↗

Uptake of lactoferrin by the liver. I. Role of the reticuloendothelial system as indicated by blockade experiments.

When 125I-labeled human lactoferrin was injected intravenously into mice it was rapidly taken up by the liver, where 75% of the dose was recovered after 15 minutes. The inhibition curve with unlabeled lactoferrin showed that the fates of labeled and unlabeled protein were similar and that the uptake capacity was saturable by milligram quantities of protein per gram of liver, suggesting the existence of numerous specific binding sites. The presence of these sites on the reticuloendothelial system was indicated by the blocking effect of dextran sulfate and latex particles. Fucoidin (fucan sulfate), which is used in the study of receptors specific for fucose, was found to inhibit the uptake of goat red blood cells as well as lactoferrin. Therefore, the inhibition exerted by fucoidin on the uptake of lactoferrin could be mediated by blockade of the reticuloendothelial system and not necessarily by competition for fucose receptors. These data indicate that the report by others that lactoferrin was taken up by a fucosyl receptor on hepatocytes is incorrect. The competition curve obtained when mouse lactoferrin was injected with its human homologue indicated that both proteins reacted with the same binding sites. However, a significant part of mouse lactoferrin was found to be taken up by the kidneys. Hepatic and renal uptakes were both reduced by prior injection of dextran sulfate.

Animals↗

Vascular clearance by the reticuloendothelial system--measurements using two different-sized albumin colloids.

Normal and reticuloendothelial system (RES) stimulated rats were examined with dynamic liver RES scintigraphy using a computerized gamma camera. 99Tcm-labelled albumin colloid, albures (radius 250 nm) or nanocoll (radius 25 nm), or both were used as test substances to study the kinetics of vascular clearance after RES stimulation. Registrations were made of 30 s per frame for 5 min and 300 s per frame for 15 min or 25 min and a region of interest (ROI) was indicated over the liver. Whole body and liver RES clearance rate constants (k) were calculated from the liver uptake vs time curve. Liver parenchyma blood flow was estimated with 133Xe washout technique. The blood clearance rate constant of albures in non-activated rats was twice that for nanocoll (1.08 +/- 0.05 vs 0.49 +/- 0.02 10(-2)s-1). There was no mutual interaction between the two colloids, implying that they may be eliminated from the blood-stream by slightly different processes. In zymosan-stimulated animals, nanocoll given in a single injection showed a significantly increased k-value. Neither the albures clearance rate constant nor the nanocoll/albures k-value ratio revealed RES macrophage activation. By contrast the nanocoll/albures ratio, calculated for the liver, rose significantly. The final colloid uptake in the liver revealed RES macrophage activation. No changes in liver parenchyma blood flow per g tissue could be registered after administration of zymosan. The nanocoll and albures colloid particles did not impair the normal liver parenchyma blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗

Complement-mediated delay in immune complex clearance from the blood owing to reduced deposition outside the reticuloendothelial system.

The effect of serum complement upon the blood clearance rate and tissue distribution of intravenously injected small immune complexes formed between 125-labelled dinitrophenyl (DNP)-conjugated human serum albumin and rabbit IgG-anti-DNP antibodies was studied in mice. Immune complexes formed in the absence of complement (i.e. in phosphate-buffered saline or in the presence of complement-depleted serum from mice treated with cobra venom factor) were cleared from the blood at a higher rate than was the antigen injected alone. In contrast, immune complexes formed in the presence of fresh normal mouse serum were cleared from the blood at the same rate as was the native antigen. Immune complexes formed in the presence of complement were eliminated mainly by the liver. The complexes formed in the absence of complement also became located to the liver to approximately the same extent, but an even larger proportion of these immune complexes was deposited outside the reticuloendothelial system. It is concluded that serum complement may inhibit IgG-mediated clearance of antigen, probably by increasing the solubility of the complexes, thereby reducing the risk of deposition outside the reticuloendothelial system.

Animals↗

Lipid emulsions and reticuloendothelial system function in healthy and burned guinea pigs.

The effect of total parenteral nutrition (TPN) regimens containing various quantities of long-chain triglyceride (LCT) and medium-chain triglyceride (MCT) emulsions on bacterial clearance and organ sequestration was evaluated in healthy and burned guinea pigs. In healthy guinea pigs, increasing the LCT component of TPN to 75% or greater of the nonprotein calories resulted in hepatomegaly, splenomegaly, a significant reduction in the sequestration of intravenously administered Pseudomonas aeruginosa by the liver and spleen, and a markedly increased clearance of bacteria into the lung. In burned guinea pigs, replacement of LCT with MCT emulsions at 75% of the nonprotein caloric intake reduced the sequestration of bacteria in the lung and restored to normal hepatic and splenic uptake. These results suggest that LCT emulsions at 75% of nonprotein calories result in reticuloendothelial system overload and increased bacterial sequestration in the lungs in normal and burned animals. In contrast, administration of MCT emulsions to the burned animal is less likely to result in increased pulmonary sequestration and decreased hepatic or splenic reticuloendothelial system function.

Animals↗