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Hemolysis following thermal injury and depression of reticuloendothelial system phagocytic function.

Previous studies have demonstrated that the injection of homologous hemolyzed blood, and reticuloendothelial system (RES) clearance of the erythrocyte membrane debris, depress RES phagocytic function and increase shock susceptibility. This study was carried out to determine if the degree of intravascular hemolysis following experimental thermal injury was comparable to the dose of hemolyzed blood required to depress RES function. The IV injection of graded doses of hemolyzed blood into rats demonstrated that 0.2 mg/100 gm of hemolyzed blood was the minimum dose of hemolyzed blood which would cause an RES depression. This volume of hemolyzed was equivalent to 2.8% of the blood volume of the animals studied. Hemolysis was assessed from the plasma hemoglobin and blood volume following graded thermal injury in anesthetized animals. Thermal injury which caused an 80% mortality rate was associated with the acute hemolysis of 3.1% of the blood sufficient erythrocyte membrane debris to induce RES depression and therapy impair host defense.

Animals↗

Effect of hepatectomy on the reticuloendothelial system of septic rats.

The purpose of this study was to evaluate the function of the reticuloendothelial system (RES) of sham hepatectomy and 20% and 50% partial hepatectomy (PH 20%, PH 50%), with or without cecal ligation and puncture-induced sepsis. The animals were injected with 51Chromium sheep red blood cells (SRBC) at 72 hours. SRBC half life (T1/2) was measured as an index of RES function and the percentage distribution of SRBC in liver, lung, and spleen was calculated. T1/2 was significantly prolonged in PH 50% rats and was associated with decreased radioactive uptake by the liver. Mortality was nil in the control groups and markedly increased in the presence of sepsis. The results suggest that decreased RES function following hepatectomy is dependent upon the proportion of liver removed and that sepsis further increased the mortality of hepatectomized animals.

Animals↗

Human granulocyte and reticuloendothelial system function during intralipid infusion.

In six patients, the phagocytic and catabolic functions of the RES (reticuloendothelial system), as measured by using 125I-microaggregated human serum albumin as a test substance, were not affected by Intralipid infusion. The nitroblue tetrazolium (NBT) reduction of granulocytes, the NBT reduction and the bacplasma, was significantly lower in eight patients during Intralipid infusion than before this treatment. When heat-killed E. coli were added for phagocytic stimulation in vitro, the same result was obtained only in the absence of plasma. The bactericidal capacity of granulocytes was significantly decreased in six patients during Intralipid infusion. When Intralipid was added in vitro to granulocytes, the NBT reduction, and the bactericidal capacity of these cells were decreased and the effect was mainly dose-dependent. Electron micrographs show that granulocytes phagocytize Intralipid. The loading of granulocytes with lipid particles may block the engulfment of bacteria and may be a reason for the decreased bactericidal capacity of these cells. An influence exerted by the lipid on the cell membrane is the most conceivable reason for the decreased NBT reduction.

Adult↗

Reticuloendothelial system and glomerular deposition of heat-aggregated human IgG.

The influence of functional impairment of reticuloendothelial system on glomerular deposition of heat aggregated human IgG (HAIgG) was studied. I-125 HAIgG was injected to mice treated either with dextran-containing 0.9% saline or with the saline alone. The HAIgG clearance rate from the blood decreased in the dextran-treated mice. The chronologically measured HAIgG contents in the liver, spleen and glomeruli increased in the dextran-treated animals. Immunofluorescent technique also demonstrated an increase in HAIgG and host C3 in the glomeruli. The glomerular hypercellularity was not demonstrated morphologically. Assuming that the function of the hepatic Kupffer cells principally affect the clearance rate of the foreign macromolecules from the blood, it is likely that the dextran administration impaired the function of these cells to digest the phagocytosed HAIgG, and that consequently the injected HAIgG stayed longer in the blood. Thus, increased supply of the HAIgG from the blood and/or the dextran-induced reduction of digesting function of the mesangial cell per se might have led to the accumulation of glomerular HAIgG. We suggest, therefore, that even small amount of immune complex may induce immune complex-mediated glomerular lesion, when associated with long lasting functional impairment of the Kupffer cells.

Animals↗

Immunological responses to fed protein antigens in mice. IV. Effects of stimulating the reticuloendothelial system on oral tolerance and intestinal immunity to ovalbumin.

We have studied the role of the reticuloendothelial system (RES) in intestinal and systemic immunity in mice immunized orally with ovalbumin (OVA). Stimulation of the RES by oestradiol completely prevented the induction of systemic tolerance normally found in mice fed 25 mg OVA and this applied both to humoral immunity and delayed-type hypersensitivity (DTH). In addition, an active DTH response could be detected in the mucosa and mesenteric lymph nodes (MLN) of oestradiol-treated, OVA-fed mice on oral challenge with OVA. Oestradiol had no direct effect on lymphocyte function and we propose that RES activation may be one mechanism which predisposes to small intestinal disease associated with food hypersensitivity.

Administration, Oral↗

Technetium 99m sulfur colloid scintigraphy to evaluate reticuloendothelial system function in dogs with portasystemic shunts.

In a retrospective study, technetium 99m sulfur colloid scintigraphy was used to evaluate reticuloendothelial system function in 61 dogs with single congenital and 40 dogs with multiple acquired portasystemic shunts. Whole body reticuloendothelial function was measured by calculating the plasma clearance rate constant from a dynamic study of liver uptake of 99mTc sulfur colloid. Relative liver, spleen, and lung uptake, and a ratio of hepatic:extrahepatic uptake were measured on static equilibrium images. Results were compared with those of a group of 26 normal dogs. Compared with values for the group of normal dogs, the plasma clearance rate constant, relative liver uptake, and hepatic:extrahepatic uptake ratio were significantly decreased, and relative spleen and lung uptake were significantly increased in dogs with portasystemic shunts (P < .0001). The only significant difference between dogs with single congenital versus multiple acquired shunts was that the relative splenic uptake was higher in the former group (P < .0002). Based on these results, we concluded that dogs with portasystemic shunts have significantly impaired reticuloendothelial function. The primary cause of this dysfunction is likely a reduction in effective liver blood flow. Increases in spleen and lung reticuloendothelial activity did occur, but only partially compensated for the reduction of liver reticuloendothelial activity. Possible mechanisms for the increased spleen and lung uptake are discussed.

Animals↗

MECHANISMS OF ENDOTOXIN TOLERANCE. II. RELATIONSHIP BETWEEN ENDOTOXIN TOLERANCE AND RETICULOENDOTHELIAL SYSTEM PHAGOCYTIC ACTIVITY IN MAN.

Healthy male volunteers were rendered tolerant to the pyrogenic and toxic activities of bacterial endotoxin by daily intravenous injections. Five subjects were given 0.5 microg Salmonella typhosa endotoxin for 7 days; four subjects were given Pseudomonas endotoxin, increasing over a period of 30 days from 25 to 250 microg. Reticuloendothelial system (RES) phagocytic activity was assessed by serial measurements of the clearance of I(131)-labeled aggregated human serum albumin. In no subject was an increase in RES phagocytic activity detectable. Such negative findings could not be attributed to decreased RES blood flow.-Additional studies on the pyrogenic responses of man to various schedules of endotoxin administration revealed: (a) Hyperreactivity of some subjects to a second injection of endotoxin administered 24 hours after the initial dose; (b) prevention of such hyperreactivity by plasma from donors tolerant to a heterologous endotoxin, but not from normal donors; (c) reduced reactivity to a second injection of endotoxin given 7 days after the initial dose; (d) reversal of induced tolerance by administration of half the dose of endotoxin followed 2 hours later by the second half; (e) reversal of induced tolerance 24 hours after administration of a heterologous endotoxin; (f) enhanced dermal reactivity to endotoxin induced inflammation during tolerance. The observations are consistent with the hypothesis that tolerance to the pyrogenic activity of endotoxin in man is not based upon generalized enhancement of RES phagocytic activity or exhaustion of host reactivity but rather involves the participation of specific antibody which assists the RES in the clearance and inactivation of the endotoxin molecule.

Antigen-Antibody Reactions↗

Effect of a perfluorocarbon emulsion (Fluosol-DA) on reticuloendothelial system clearance function.

To study the effect of a perfluorocarbon oxygen transport emulsion (Fluosol-DA) on reticuloendothelial system (RES) function, we measured the blood clearance of human erythrocytes transfused to rats. Compared with saline treatment, Fluosol-DA at 30 ml/kg doses significantly increased both the percent 20-hour blood recovery (mean 8.9% +/- 2.7 SEM vs 1.3% +/- 0.25 SEM) and 51Cr t1/2 survival (mean 14.0 hours +/- 2.7 SEM vs 3.5 hours +/- 0.33 SEM) of the human red cells. This suppression of RES clearance function was transient and no longer detectable seven days after single Fluosol-DA doses. The Fluosol-DA-induced RES block was about three times greater than that obtainable with 4 g/kg of a soybean oil emulsion used for clinical hyperalimentation. On the other hand, the effect of ethyl palmitate (0.5 g/kg), a potent but toxic RES blocker, was 3.5 times greater than that of Fluosol-DA in this test system. If Fluosol-DA also induces RES block in humans, this emulsion could be explored as a therapeutic RES blocker in certain immune cytopenias.

Animals↗

Effect of red blood cells and red blood cell ghosts on reticuloendothelial system function.

Previous studies have shown that hepatic phagocytosis of red blood cell (RBC) stroma can depress reticuloendothelial system (RES) phagocytic function and increase susceptibility to shock. Since the RBC stroma used in these experiments contained substantial amounts of adherent hemoglobin, the present study was carried out to evaluate the role of the hepatic uptake of RBC membrane material on RES phagocytic function and susceptibility to endotoxin shock in rats. Neuraminidase-treated RBC which contained normal amounts of hemoglobin and RBC ghosts which were hemoglobin-free were used. Both preparations were removed from the circulation primarily by the liver. RES phagocytic function was depressed following the hepatic uptake of 29 X 10(8) neuraminidase-treated RBC and 26 X 10(8) RBC ghosts. RES uptake of neuraminidase-treated RBC was associated with an increase in susceptibility to endotoxin shock, but RBC ghosts did not affect shock susceptibility. Thus, RBC ghosts and intact RBC are equally effective in depressing RES phagocytic function, but RBC ghosts did not affect susceptibility to endotoxin shock.

Animals↗

Oversaturation status of reticuloendothelial system following cardiopulmonary bypass.

In the past, it was generally believed that the phagocytic function of the reticuloendothelial system (RES) was depressed after cardiopulmonary bypass (CPB), but several investigators reported differing results. Therefore, this study was performed to determine the effect of CPB on RES function, experimentally and clinically. Six dogs undergoing CPB (CPB group) were compared with an identical number of dogs subjected to thoracotomy without CPB (control group). A lipid emulsion test was performed in all dogs before and after the surgical procedure to measure RES phagocytic function. Any ultrastructural changes in Kupffer cells were observed by electron microscopy. In both groups, the RES phagocytic index showed a significant decline after surgery. However, comparison of the 2 groups revealed that there was a significantly greater decrease in the CPB group (p < 0.05). Electron microscopy of the Kupffer cells showed that the number of phagosomes, especially those containing deformed erythrocytes, increased after CPB. Twenty patients undergoing cardiac surgery requiring CPB (Group A) and 8 patients undergoing pulmonary resection (Group B) were studied. RES phagocytic function was determined 3 days prior to surgery and 3 days postoperatively using the lipid emulsion test. No significant difference was observed in the preoperative phagocytic indices between the 2 groups. The phagocytic function remained almost unchanged in Group A on the third postoperative day, compared with the preoperative value, but it increased significantly in Group B on the third postoperative day, compared with the preoperative value. The intergroup difference was significant on the third postoperative day (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Reticuloendothelial system Fc-receptor function in patients with immune thrombocytopenia after treatment with high dose intravenous immunoglobulin.

Reticuloendothelial system Fc-receptor (FcR) function was measured in 4 healthy controls and 9 patients with immune thrombocytopenia before and after therapy with high dose i.v. gammaglobulin (HDIg). Idiopathic thrombocytopenic purpura (ITP) was diagnosed in 5 patients. 2 patients with hemophilia A, 1 with acute tuberculosis and 1 with psoriasis vulgaris had thrombocytopenia that clinically resembled ITP. 4 out of 9 patients received prednisone prior to or during the study. FcR blockade was observed only in patients with ITP not receiving prednisone. In all other patients, HDIg did not induce a measurable FcR blockade. However, all except 1 patient (with acute tuberculosis) showed a marked rise in platelet counts for 2 to 12 wk. This is consistent with therapeutic efficacy of HDIg in various clinical settings of immune thrombocytopenia. All platelets were fully hemostatic and clinically no difference could be observed. This indicates that the effect of HDIg cannot be due to FcR blockade alone.

Adolescent↗

[Extrapulmonary tuberculosis with involvement of the reticuloendothelial system and secondary lupus vulgaris].

The authors describe a case of extrapulmonary tuberculosis with affection of the reticuloendothelial system in a 59-year-old female patient. After successful treatment the findings in the spleen, bone marrow and the laboratory results had normal levels. The authors draw attention to the diagnostic difficulties. They were able to confirm the diagnosis only by histological examination of biopsy from the pelvic bone. An interesting finding was eruption of lupus vulgaris on the legs in the course of treatment. The authors discuss some aspects of the disease and its differential diagnosis.

Bone Marrow Diseases↗

Establishment of a multi-dose study of chondroitin sulfate iron colloid for evaluation of the reticuloendothelial system function.

The assay system of chondroitin sulfate iron colloid (CSFe) was established to evaluate the reticuloendothelial system (RES) function in individual rabbits. In the multi-dose study of CSFe, CSFe was repeatedly administered to each individual rabbit with increasing doses (0.6, 1.2, 2.4, 6.0 mg/kg) at set intervals. Blood samples were serially collected after injection of CSFe and the concentration of CSFe in serum was directly measured as an iron concentration by modifying the previously described assay method [1] to minimize the sample volume. The clearance rate of CSFe at each injected dose was computed by the least-squares method and the double-reciprocal plotting of the doses against the phagocytic velocities by the Lineweaver-Burk method was obtained in each rabbit. The maximum phagocytic velocity (Vmax) and the CSFe concentration producing 1/2 Vmax (Kp) obtained in ten rabbits were 0.129 +/- 0.025 mg/kg per min and 0.417 +/- 0.121 mg/kg (mean +/- S.D.), respectively. The results obtained from this multi-dose study were comparable to our previous results obtained from the mean values of five groups given different doses [1]. The clearance rates of CSFe (0.6, 1.2, 6 mg/kg) decreased after the co-injection of 80 mg/kg of carbon colloid. The calculated Vmax and Kp in 29 rabbits were 0.125 mg/kg per min and 1.167 mg/kg. The Kp was apparently greater than that of the control (Vmax = 0.128 mg/kg per min, Kp = 0.421 mg/kg). Carbon colloid (80 mg/kg) was injected to six rabbits after the completion of the first multi-dose study of CSFe and then the second multi-dose study of CSFe was repeated after 24 h. No differences were found in Vmax and Kp between the two studies as were in the control group (10 rabbits) where saline was injected instead of carbon colloid. These results indicated that carbon colloid (80 mg/kg) gives a competitive and reversible inhibition on the RES. This multi-dose study of CSFe may be applicable for a bed-side analysis of the RES function in a patient.

Animals↗

Effect of platelet activating factor on reticuloendothelial system function.

The effect of platelet activating factor (PAF) injections on the uptake of 99mTc-SC (99mTc-SC (99mTc-sulphur colloid) was determined in vivo. PAF (2 micrograms) injected intravenously into unanaesthetized, unrestrained rats was associated with the development of lesions in the small intestine and alteration of 99mTc-SC uptake in vivo. 99mTc-SC uptake into the lung was increased while spleen uptake was decreased. Pretreatment of the animals with a PAF antagonist, SRI-64-441, prevented the intestinal lesions and alterations of 99mTc-SC uptake. Macrophages, isolated from lung lavage of the PAF-treated rats, demonstrated a decreased generation of hydrogen peroxide in vitro. The present results suggest that, in addition to its other effects on the immune system, PAF can also alter the in vivo phagocytic activity of the reticuloendothelial system in the rat.

Animals↗

[The function of the reticuloendothelial system studied with the use of radioactive colloids].

A new method for the interpretation of data obtained during radionuclide investigation of the reticuloendothelial system (RES) was proposed. It was based on a detailed description of the mechanism of reticuloendothelial extraction of a colloid injected intravenously. A model developed for this purpose included the main stages of radioactive colloid transport. The paper also represented a comparative analysis of the results of clinical examination of the controls and patients with liver cirrhosis. A 4-fold decrease of the blood flow in portal liver cirrhosis was noted as compared with normal mean indices in a 2-fold decrease in the specific blood supply of cells of the RES and in a 2-fold decrease in its volume. An increase in phagocytosis rate in patients with liver cirrhosis needs further verification.

Algorithms↗

Mechanism of impaired iron release by the reticuloendothelial system during the hypoferremic phase of experimental Neisseria meningitidis infection in mice.

Hypoferremia, the reduction of plasma transferrin iron levels during infection, has been shown to control Neisseria meningitidis infection in mice. The exact nature of the mechanism that regulates this response has been obscure. We have previously shown that hypoferremia does not result from an accelerated removal of iron from the plasma transferrin pool. In this study, we have examined the processing of iron by the reticuloendothelial system during infection. Normal and hypoferremic meningococcus-infected mice were injected with 59Fe-labeled erythrocytes. Kinetics of uptake and redistribution of the label indicated that during the hypoferremic phase of the infection, reticuloendothelial system-processed iron was not returned to the plasma transferrin pool. Fractionation of hepatic cellular compartments showed that this impaired release of iron resulted from a preferential incorporation of heme-derived iron into the intracellular ferritin pool during the hypoferremic phase of the infection. These findings indicate that this withholding of iron within the intracellular pool leads to hypoferremia and therefore denies the extracellular pathogen its essential iron.

Animals↗

The adaptive response of the reticuloendothelial system to major liver resection in humans.

OBJECTIVE: To evaluate the contribution of the liver to total circulatory reticuloendothelial system (RES) phagocytosis capacity in patients undergoing liver resection and to compare it with values in end-stage chronic liver disease. SUMMARY BACKGROUND DATA: The mechanism whereby major liver resection is associated with a high incidence of infection is unknown. Significant impairment of RES phagocytosis has been described in liver failure, rendering such patients susceptible to infection; and we hypothesized that similar impairment might occur following major liver resection. METHODS: A prospective study was conducted in which Tc-albumin microspheres blood clearance served as a parameter for RES phagocytosis and was studied together with indocyanine green blood clearance, actual liver volume measured by three-dimensional image analysis, and a clinical score of hepatic dysfunction in 17 patients undergoing liver resection and in 8 patients with end-stage chronic liver disease assessed for liver transplantation. RESULTS: When expressed relative to volume unit of residual liver, microspheres clearance increased significantly in the immediate postoperative period (day 1) following major (0.009% versus 0.022% min(-1) mL(-1), P < 0.001), but not minor liver resection. In contrast, the absolute rate of microsphere clearance decreased following major resection (15% min(-1) versus 10% min(-1), P < 0.001) and was comparable with the rate observed in end-stage chronic liver disease (9% min(-1)). This decrease in circulatory microspheres clearance after resection paralleled a decrease in indocyanine green clearance (R2 = 0.511, P = 0.006), and there was a trend for those with moderate liver dysfunction to have lower microspheres clearance rates (P = 0.068). CONCLUSION: Preservation of a minimum volume of functioning liver is a prerequisite for adequate RES phagocytosis capacity, and failure of this system may predispose patients undergoing major liver resection to infection as observed in clinical studies.

Adaptation, Physiological↗