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PubMed1980

Immune complexes and reticuloendothelial system function in human disease.

The interrelation between the presence of circulating antigen-antibody complexes and the functional status of reticuloendothelial system Fc-receptors was studied in patients with systemic lupus erythematosus and Sjogren's syndrome. Both groups of patients had a high prevalence of circulating immune complexes as detected by the 125I-Clq binding assay and the Raji cell radioimmune assay. A number of patients with both diseases were found to have abnormal reticuloendothelial system Fc-receptor function, as measured by the clearance of IgG-sensitized, 51Cr-labeled autologous erythrocytes. In patients with systemic lupus erythematosus there was a high correlation between the presence and levels of immune complexes and abnormal clearance rates. In Sjogren's syndrome on the other hand there was no correlation between the presence or levels of immune complexes and clearance rates. In this disease patients with normal rates of clearance tended to have disease limited to exocrine glands, while patients with abnormal clearance had evidence of more widespread tissue damage. These findings are consistent with the hypothesis that defective reticuloendothelial system function may lead to the prolonged circulation of immune complexes, thereby contributing to tissue damage.

Antigen-Antibody Complex↗

PubMed1982

Mechanism of hyperinsulinemia after reticuloendothelial system phagocytosis.

Endocytic loading of the reticuloendothelial system (RES) results in acute hyperinsulinemia and functional hyperinsulinism. Colloidal carbon blockade of the RES in rats resulted in elevations of both portal vein and systemic serum immunoreactive insulin and increases in the hepatic portal vein insulin glucose ratios. Two mechanisms for the hyperinsulinemia were evaluated: 1) decreased removal of insulin by the postendocytic liver and 2) increased secretion of insulin by the isolated perfused pancreas. Colloidal carbon blockade did not alter removal of 125I-insulin as evaluated in the isolated perfused rat liver. Pancreases from postendocytic donor rats when perfused according to the technique of Grodsky manifested enhanced insulin secretion. Macrophage culture-conditioned media enhanced glucose-mediated insulin secretion both as assayed in vivo and in the isolated perfused rat pancreas. The data suggest that postendocytic activated macrophages secrete a monokine that alters insulin release and thus produces the hyperinsulinemia of RES blockade. The acronym MIRA for macrophage insulin-releasing activity is proposed for the monokine.

Animals↗

PubMed1991

Increased Fc-receptor-mediated clearance via reticuloendothelial system in patients with nephrotic syndrome.

Reticuloendothelial phagocytic cell function, which is an important participant in host defense, was investigated by studying the Fc-receptor-mediated clearance of IgG-anti-RhD-sensitized radiolabelled autologous erythrocytes in patients with nephrotic syndrome known to have an increased risk of infectious complications due to hypogammaglobulinemia. Patients with serum IgG concentrations less than 500 mg/dl had a significantly accelerated Fc-receptor-mediated clearance (t1/2 = 52 +/- 3.6 min) compared to patients with IgG levels greater than 500 mg/dl (t1/2 = 93 +/- 17 min) or healthy controls (t1/2 = 100 +/- 7.5 min). Serum IgG concentrations correlated significantly with Fc-receptor-mediated clearance (t1/2: r = 0.70; p = 0.035) in patients with nephrotic syndrome. These results indicate that Fc-receptor-mediated clearance by the reticuloendothelial system is enhanced in patients with nephrotic syndrome with low serum IgG concentrations and may, at least in part, compensate for reduced opsonic antibody concentration.

Adult↗

PubMed1994

Membrane modification by negatively charged stearyl-polyoxyethylene derivatives for thermosensitive liposomes: reduced liposomal aggregation and avoidance of reticuloendothelial system uptake.

In order to avoid reticuloendothelial system (RES) uptake and prolong systemic circulation of cisplatin (CDDP)-encapsulating thermosensitive liposomes, stearylpolyoxyethylene (POE) derivatives [SnC, stearyl-O-(CH2CH2O)n-CH2COONa] were incorporated as membrane modifiers into lipid bilayers composed of dipalmitoylphosphatidylcholine (DPPC) and distearoylphosphatidylcholine (DSPC). The incorporation of S2C, S5C, S10C or S15C [lipid/SnC = 10/2 (w/w)] greatly reduced liposomal aggregation without impairing liposomal stability. After being intravenously administered to rats, the liposomes remained longer in the systemic circulation and showed lower RES levels than the control liposomes. When incorporated into liposomes [DPPC/DSPC = 7/3 (w/w)], S10C provided the greatest increase in systemic circulation time and the RES-avoiding activity among the modifiers tested. The systemic elimination rate (the ratio of the percent of the dose systemically eliminated to the AUC of the liposome level) for this type of liposome was 0.24/hr, about one fourth the rate for the control liposomes, and the RES uptake rate (the ratio of the percent of the dose taken up by the RES to the AUC) was 0.04/hr, one seventh the rate for the control liposomes. The RES uptake rate for S10C 7/3-liposomes was similar to the rate reported for GM1 liposomes, although the systemic elimination rate was double that for the GM1 liposomes. The obtained RES avoidance activity can be attributed to decreased liposomal aggregation and increased surface hydrophilicity. This type of thermosensitive liposome should be more useful in hyperthermia-mediated targeted tumor drug delivery systems than the thermosensitive liposomes without the modifiers to avoid RES uptake.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1984

[Biotesting of a burn toxin on mice with reticuloendothelial system block].

Experiments on mice with reticuloendothelial system blockade were made to assay the toxic properties of the preparations obtained from the skin of burn and normal rats. As regards the activity level the preparations can be classified with either highly toxic or little toxic. Analysis of the dose-response dependence indicates that toxicity of the extracts is accounted for by at least two different toxins.

Animals↗

PubMed1979

Sjögren's syndrome: a defect in reticuloendothelial system Fc-receptor-specific clearance.

To determine the functional status of reticuloendothelial system Fc receptors in patients with Sjögren's syndrome, we studied the rate of clearance from the circulation of 51Cr-labeled IgG-sensitized autologous erythrocytes in 19 patients. Fc-receptor-mediated clearance was abnormal in 12 of the 19 patients, with half-lives ranging from 80 to 356 min. There was a significant correlation between clearance rates and clinical manifestations of disease. Clearance rates tended to be normal in patients with disease limited to exocrine glands and abnormal in patients with widespread disease. In contrast, there were no correlations between the rate of clearance of IgG-sensitized erythrocytes and serum immune complex levels, serum complement component levels, or rheumatoid factor titers. The striking correlation between clearance rates and disease manifestations suggests that decreased clearance of immune complexes by defective reticuloendothelial system Fc receptors may contribute to disease pathogenesis.

Adult↗

PubMed1978

Prevention of liver reticuloendothelial systemic host defense failure after surgery by intravenous opsonic glycoprotein therapy.

Depression of the reticuloendothelial system (RES) was observed in rats following operative trauma consisting of laparotomy and jejunal enterotomy. This RES depression was manifested as a significant impairment in the phagocytic clearance of intravenously injected blood-borne test colloid mediated by a decline in hepatic Kupffer cell phagocytosis. Reticuloendothelial systemic host defense depression was correlated with a significant decline in bioassayable and immunoreactive opsonic alpha(2)SB glycoprotein concentration over a 1-3 hr postoperative period with rebound elevation in opsonic activity by 24 hr postsurgery. Intravenous administration of purified opsonic alpha(2)SB glycoprotein at the end of the operation prevented postoperative opsonic deficiency and restored normal hepatic RES phagocytic function. These studies coupled with previous observations in patients following surgery or after severe multiple trauma suggest that reticuloendothelial depression during and after operation mediated by opsonic deficiency may lead to a precarious imbalance between systemic host defense and the dissemination of blood-borne foreign and effete particulate matter such as injured platelets, fibrin microaggregates and immune complexes. Immunoreactive serum opsonic alpha(2)SB glycoprotein determinations may serve as a valuable index of hepatic RE clearance capacity and opsonin therapy may potentially be a selective means to augment systemic host defense.

Animals↗

PubMedDate not supplied

Effect of acute burn trauma on phagocytic activity of the reticuloendothelial system in rats.

The effect of acute burn trauma on phagocytic activity of the reticuloendothelial system measured in vivo with technetium 99m sulfur colloid was examined in rats subjected to acute burn trauma. After the scald injuries (10-second, full-thickness burns) were induced, a reduction in phagocytic activity by the spleen took place with an accompanying increase in the uptake of colloid material by the lungs. Uptake of colloid material by the liver was essentially unchanged. These uptake changes, observed within hours after the inducement of acute burn trauma and apparently continuing for 7 days after burn injury, may explain, in part, the development of septicemia in patients with burns because altered phagocytic activity of the reticuloendothelial system can result in subsequent overabundance of microorganisms and bacteria in the blood.

Animals↗

PubMed1980

Phagocytosis of inert particles in the reticuloendothelial system in rats with experimental insulinopenic diabetes.

Phagocytosis of inert, radioactive gold particles in the reticuloendothelial system in rats in the case of experimental insulinopenic diabetes was studied. In the spleen, phagocytosis was seen to have fallen to a relatively low level after four weeks from the induction of diabetes. In the liver, there was noted a reduction of phagocytosis per gram of organ, though it remained the same for the total organ which in the case of diabetes mellitus increases in weight relative to body weight. This difference in reaction of the reticuloendothelial system in the liver and spleen has also been observed in mice with tumors. The importance of the findings of the present study for increased sensitivity to infections of poorly controlled diabetic patients is discussed in greater detail.

Animals↗

PubMed1982

A serial study of splenic reticuloendothelial system Fc receptor functional activity in systemic lupus erythematosus.

A serial study of reticuloendothelial system splenic Fc receptor function was undertaken in 13 patients with systemic lupus erythematosus (SLE). Fc receptor function was assessed by measuring the clearance half times of IgG-sensitized 51Cr-labeled autologous erythrocytes from the circulation. Prolonged clearance half times were initially detected in all patients, and the magnitude of the clearance defect was significantly correlated with disease activity (P less than 0.01, Spearman rank correlation) and immune complex levels (P less than 0.01). Clinical course and changes in receptor functional activity over time were found to be significantly correlated. Clearance half-times tended to return to normal in all 11 patients who clinically improved. The clearance half-time remained unchanged in 1 patient whose disease activity was stable, and it worsened in 1 patient whose illness flared. Levels of immune complexes also changed concordantly with clearance half-times and disease activity. These studies underscore the interrelationship between the presence of circulating immune complexes, defects in Fc receptor function that might lead to prolonged circulation of these complexes, and disease activity in SLE.

Adult↗

PubMed1988

Function of reticuloendothelial system in splenectomised thalassemics.

The activity of reticuloendothelial system (RES) was estimated in 19 patients with beta-thalassemia major, 20 +/- 4 years old, who had undergone successful splenectomy 6 +/- 5 years previously. The kinetics of 125I denatured human serum albumin in low and large doses was applied for this purpose and the parameters derived (effective RES blood flow-ERBF- and maximum phagocytic capacity-PCmax) were compared to those of nonsplenectomized thalassemics, detected in previous works, as well as to those of 13 healthy controls. In splenectomised thalassemics both parameters of RES activity were found significantly lower than those of nonsplenectomized patients (p less than 0.001). Compared to those of healthy controls, PCmax of splenectomised thalassemics was found not to be significantly different, while ERBF was significantly lower (p less than 0.001). No correlation was noted between the above parameters of RES function and the age of the patients, the age at which splenectomy was performed, the time lapsed since the operation, the amount of blood transfused to the patients after splenectomy or their serum ferritin levels. A pilot study performed in 6 out of the 19 splenectomised patients did not reveal any effect of blood transfusion on RES function parameters, by contrast to observations in nonsplenectomized thalassemics. The results of this study suggest that in splenectomised thalassemics the remaining RES reacts to the continuing hemolytic stimulus in a manner different than that of splenic RES of nonsplenectomized patients and account for, at least in part, the predisposition of the former group to infections.

Adolescent↗

PubMed1979

Defective reticuloendothelial system Fc-receptor function in systemic lupus erythematosus.

To determine whether reticuloendothelial-system immunospecific Fc-receptor function is abnormal in patients with systemic lupus erythematosus, we studied the clearance of IgG-sensitized 51Cr-labeled erythrocytes by these splenic macrophage membrane receptors in 15 untreated patients. Fc-specific clearance rates were strikingly abnormal in 13 of 15 patients (half-times ranging from 80 to 2256 minutes, P less than 0.001 as compared to controls). Abnormal clearances correlated with immune-complex levels (as measured by the C1q-binding assay) and with disease activity. C1q-binding activity and anti-DNA titers also correlated with disease activity. The correlations of C3, C4, CH50 and factor B with abnormal clearance and disease activity were weaker or nonexistent. The significant correlations among clearance, disease activity and C1q-binding activity suggest that the defect in Fc-receptor function may lead to the prolonged circulation of immune complexes, thereby contributing to tissue deposition and damage.

Adult↗

PubMed1975

[Effect of the quality of various vegetable oil emulsions on phagocytotic activity of the reticuloendothelial system in the rat].

In the liver, reticuloendothelial cells make up 35 p. 100 of the total cellular population. The characterization of the reticuloendothelial system (RES) is its phagocytic activity. Certain fatty acids and lipids produce stimulation or depression of phagocytic function. In the present study, the phagocytic activity of the RES has been evaluated 3 days after oral (15 g/kg) and intravenous (1, 5 g/kg) treatments of male rats with emulsions of peanut, canbra, soyabean, olive and rapeseed oils. The distribution of particle sizes of all suspensions were made microscopically. Phagocytic function was measured by the blood clearance of colloidal carbon injected intravenously; the phagocytic index was calculated from the formula: log C=Kt + log C0 where C and C0 were carbon concentrations in standard volumes of blood removed from the animals at times t and t0 (in minutes). Intravenous administrations with the 5 oil emulsions significantly increased the phagocytic function of the RES. However, with oral administration, stimulation or depression of phagocytic function were dependent of many factors, among them the nature of the oil and the physical and chemical structure of the lipid emulsion. The variations in particle sizes found in emulsions make it extremely difficult to draw any comparison between their effects on the RES phagocytic capacity of rat; but difference in the distribution of various particle sizes provided an indirect approach to studying their influences on RES stimulation or inhibition. However, it is obvious that although modifications of particle sizes may alter the level of phagocytic activity induced by certain oil emulsions, they do not explain the phenomenon. The activity of phagocytic function of oil emulsions on RES cells can be related to their physical or chemical properties; the mode of esterification of the fatty acids may be an important factor. However, no evidence has been obtained which in any way correlates changes in physical or chemical properties of the studied oil emulsions with the observed differences in effects upon the RES cells. No adequate explanation of the role of these parameters in the stimulation or inhibition of phagocytic properties of RES can be made and other studies are necessary.

Administration, Oral↗

PubMed1978

[Relationship between the phagocytic inhibition of the rat reticuloendothelial system and the anticholinesterasic effect of an insecticide, Carbaryl (author's transl)].

Phagocytic activity of the reticuloendothelial system (RES) and blood cholinesterase activity were determined in male rats after veinous administrations of carbaryl and 1-naphthol, a carbaryl metabolite. The various parameters were measured 1, 24, 48 and 72 hours after administration of the following four doses per 100 g body weight : 1.875, 3.75, 7.5 and 15 mumol. 1. Results showed an inhibition of the RES phagocytic activity (clearance of colloidal carbon) after carbaryl administration; although 1.875 mumol/100 g had no effect, the other doses inhibited RES activity, blockade time being a function of the dose given. The phagocytic function had returned to normal 72 hr after carbaryl administration. 2. Reductions in spleen weight and protein content were observed together with the RES blockade. 3. At all four doses, the anticholinesterase effect was already apparent one hour after carbaryl administration. 4. 1-naphthol, one of carbaryl's chief metabolites, had no effect either on the RES or on the different parameters studied. These results show a relationship between the phagocytic inhibition of the reticuloendothelial system and the anticholinesterasic effect by carbaryl. They suggest an inhibition of some esterases of macrophages interfering with the phagocytosis.

Animals↗

PubMed2002

Gut barrier permeability, reticuloendothelial system function and protease inhibitor levels following intestinal ischaemia and reperfusion--effects of pretreatment with N-acetyl-L-cysteine and indomethacin.

BACKGROUND: Pathophysiological mechanisms and ways to intervene on intestinal barrier dysfunction following small intestinal ischaemia and prolonged reperfusion are still not fully clarified. AIMS: To evaluate the effect of oxygen free radical and prostaglandin inhibition on intestinal barrier injury following intestinal ischaemia/reperfusion. METHODS: Endothelial and epithelial barrier permeability was evaluated by clearance of radiolabelled albumin. Parameters included 125I-Escherichia coli uptake rate index, host reticuloendothelial system function and organ distribution, as well as protease inhibitor and proenzyme activities in rats subjected to small intestinal ischaemia for 40 minutes followed by 12 hours reperfusion (ischaemia/reperfusion), pretreated with N-acetyl-L-cysteine or indomethacin. RESULTS: Following ischaemia/reperfusion, endothelial and epithelial permeability increased, reticuloendothelial system activation occurred and plasma protease inhibitors were consumed. N-acetyl-L-cysteine pretreatment resulted in improved endothelial and epithelial barrier integrity, a decrease in protease inhibitor consumption and less pronounced reticuloendothelial system activation. Pretreatment with indomethacin was not effective. CONCLUSION: Oxygen free radicals seem to play an important role in the development of intestinal barrier impairment following ischaemia/reperfusion. N-acetyl-L-cystine may be a potential agent for preventing ischaemia/reperfusion damage.

Acetylcysteine↗

PubMed1990

Estimation of in vivo reticuloendothelial system phagocytic activity in rats by direct blood clearance techniques and nuclear scintigraphy.

There has been considerable interest in the examination of reticuloendothelial system phagocytic blockade. In this study, the kinetics of phospholipid liposome-mediated and intraperitoneal silica-mediated phagocytic blockade were examined using five methods of analysis of in vivo 99mTc-labeled albumin clearance and reticuloendothelial cell uptake. Two direct blood sampling techniques revealed significant impairment in 99mTc-labeled albumin clearance after treatment with silica (P less than 0.05), while liposome treatment was not associated with such impairment. A method utilizing nuclear scintigraphy for the determination of blood clearance was incapable of detecting silica-mediated blockade but demonstrated significant impairment by liposomes at 2 hr (P less than 0.001), 6 hr (P less than 0.05), and 24 hr (P less than 0.001). Gamma camera imaging methods for determination of hepatic uptake demonstrated significant (P less than 0.05) and reversible impairment of 99mTc-labeled albumin uptake by liposomes. The most promising of these techniques utilizes deconvolutional analysis of liver region of interest time-activity curves to correct for continuously changing blood concentrations of tracer and for intracellular tracer processing and catabolism. Measurements of reticuloendothelial system phagocytic activity should include methods that take into account the observed discrepancies between blood clearance determinations and reticuloendothelial cell uptake.

Albumins↗

PubMed1985

Chemical blockade of the reticuloendothelial system results in arteriolar spasms: possible role of endothelial cells.

Scattered qualitative studies in the literature suggest that the reticuloendothelial system (RES) interacts with the microcirculation to effect host defense and that chemical or pharmacologic blockade of the RES might compromise the microcirculation. With this possibility in mind, we designed experiments in rats to determine whether colloid and pharmacologic blockade of the RES could alter microvascular tone and reactivity. The effects of colloidal carbon, thorium dioxide, tripalmitin and tetracycline on reticuloendothelial system phagocytic function, mesenteric terminal arteriolar tone and arteriolar reactivity to noradrenaline and acetylcholine were examined in situ at magnifications up to 5000x. Colloidal carbon and thorium dioxide, in the doses utilized, produced complete blockade of the RES. Treatment with tripalmitin and tetracycline produced pronounced RES depression. RES blockade and depression were associated with marked reductions in terminal arteriolar lumen sizes, curtailment of capillary inflow and outflow, hyper-reactivity to the constrictor, noradrenaline, and hypo-reactivity to the dilator, acetylcholine. Close examination of the endothelial linings of the capillaries, postcapillary venules and terminal arterioles of the experimentally-treated animals indicated pronounced uptake of carbon particles in the endothelial cells, different degrees of endothelial cell swelling and often bulging into the microvessel lumens. Our findings suggest that RES-induced alterations in microvascular tone and arteriolar reactivity may be related to injury of the microvascular endothelial cells.

Animals↗

PubMed1963

PROGRESSIVE MULTIFOCAL LEUCOENCEPHALOPATHY AND PRIMARY HYPERSPLENISM. WITH A NOTE ON THE ASSOCIATION BETWEEN DISEASE OF THE RETICULOENDOTHELIAL SYSTEM AND PROGRESSIVE MULTIFOCAL LEUCOENCEPHALOPATHY.

A patient with progressive multifocal leucoencephalopathy was found to have primary hypersplenism, a benign disorder of the reticuloendothelial system. He failed to respond to conventional doses of corticosteroids. The clinical and pathological manifestations of his illness are described, and the development of the histopathological changes in the nervous system is discussed. Consideration of available data on progressive multifocal leucoencephalopathy reveals a striking association with disease of the reticuloendothelial system, the significance of which is discussed in relation to aetiology and treatment.

Brain Diseases↗