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PubMed1985

Measurements of reticuloendothelial system phagocytic activity in the rat after treatment with silica, liposomes, and cyclosporine.

Reticuloendothelial system phagocytosis was evaluated in vivo by the clearance and tissue distribution of 99mTc-albumin millimicrospheres in rats. Administration of i.p. silica 2 days prior to clearance measurement increased the half-life of millimicrospheres 24% compared with control animals (P less than 0.01). Impairment of phagocytic activity was maintained at 5 days to 22% over control values (P less than 0.01). Tissue distribution studies showed that liver uptake was reduced and splenic and pulmonary uptake was increased compared with control. Cyclosporine i.v. increased half-life by 14% 1 hr after administration )P = NS) and half-life returned to control values by 8 hr. Hepatosplenic shift was less marked than after silica treatment. Phospholipid liposomes i.v. produced prompt impairment of millimicrosphere clearance after 1 hr; half-life was prolonged 46% over control values (P less than 0.001 vs. control) and marked radiolabel shift to the spleen and lung was seen. Measurements done 18 hr after a dose of liposomes revealed an increase of 55% over control half-life (P less than 0.001). Liposomes appear to be potent, nontoxic--and, in some cases, reversible agents--for blockade of reticuloendothelial phagocytosis and examination of non-phagocytic reticuloendothelial functions. These results help to explain some of the results obtained in pancreatic islet grafting and suggest that phospholipid liposomes may be useful in this form of transplantation.

Animals↗
PubMed1996

Hepatic reticuloendothelial system dysfunction after intestinal ischemia-reperfusion.

The functional capacity of the hepatic reticuloendothelial system (RES) was studied under conditions of intestinal shock. Wistar rats underwent intestinal ischemia (60 min)-reperfusion or a sham procedure. One-half of each group received intravenous infusion of 2.6 x 10(-6) g/kg lipopolysaccharide B. Phagocytic clearance and phagocytic killing by the hepatic RES were quantitated using a double label bacteria clearance assay. Hepatic phagocytosis was unchanged 3 h after reperfusion of the ischemic intestine but hepatic killing was significantly decreased compared with the sham situation. The results were not different in animals who had received LPS B infusion. The plasma endotoxin levels correlated inversely to the hepatic killing efficiency (r = -.801) in the shocked animals given exogenous endotoxin. The decreased capacity of the hepatic RES to degrade bacteria present in the portal circulation could be an important pathophysiologic mechanism in the development of bacterial translocation.

Animals↗
PubMed1967

Reticuloendothelial system phagocytic function in patients with Hodgkin's disease.

Phagocytic function of the reticuloendothelial system as measured by the clearance of (125)I-labeled aggregated human serum albumin (AA) was studied in patients with Hodgkin's disease. Each more advanced stage of the disease was associated with more rapid clearance of the AA. Production of remission by radiation therapy or by chemotherapy was associated in some patients with slowing of the clearance rate, whereas relapse seemed to be associated with acceleration. Thus, impaired phagocytosis cannot be implicated in the several defects in immunity known to be present in Hodgkin's disease. Furthermore, determination of the clearance rate of AA in patients with Hodgkin's disease may have clinical usefulness as another indicator of extent or activity of disease.

Antineoplastic Agents↗
PubMed1976

Preparation of cross-linked human serum albumin labelled with 125I for studies of reticuloendothelial system function.

A method is described to prepare a new test substance for reticuloendothelial system (RES) function studies. Glutaraldehyde was used for the cross-linking of human serum albumin. The polymeric product was fractionated by repeated chromatography on Sepharose 6B. Cross-linked material with a particle size of approximately 18 nm, as evidenced by electron microscopy, was pooled and labelled with 125I. The surface charge of the albumin polymers, determined by agarose gel electrophoresis, was not significantly changed compared with that of the original albumin monomer. Cross-linking takes place almost entirely between the epsilon-amino groups of lysine in the albumin molecules, as confirmed by amino acid analysis. Preliminary biological tests on mice indicate that the cross-linked polymers are phagocytosed mainly by RE cells of the liver and spleen. The disappearance rate was similar to that of other RE test substances. Intravenous administration of more than 50 times the usual dose caused no deaths, indicating a very low toxicity. Trace amounts of glutaraldehyde were not detectable by gas chromatography. Judging from these experiments, this new preparation of cross-linked albumin fulfils many of the criteria stated for an ideal RES test substance.

Animals↗
PubMed1995

Effect of agents which modify reticuloendothelial system function on acute phalloidin-induced lethality and hepatotoxicity in mice.

The relationship between reticuloendothelial system (RES) function and acute phalloidin intoxication was studied in mice. Pretreatment with compounds that stimulate (zymosan) or depress (methyl palmitate and praseodymium nitrate, Pr(NO3)3) the RES resulted in protection against phalloidin-induced lethality and hepatotoxicity, as assessed by morphological analysis. However, triolein (which stimulates the RES) was ineffective against phalloidin. The timing of pretreatment with the effective compounds showed a correlation between modified in vivo RES function (phagocytosis) and protection against the toxin. The effects of pretreatment with zymosan and Pr(NO3)3 were further characterized. Hepatic damage induced by phalloidin was significantly decreased by these agents, as judged by morphological analysis as well as by serum aspartate aminotransferase and alanine aminotransferase release. This study also showed that there was no correlation between the capacity of Kupffer cells to produce nitrite and prophylaxis against phalloidin. However, liver cell proliferation was increased by zymosan and Pr(NO3)3 in parallel with protection against the toxin. Furthermore, freshly isolated hepatocytes from zymosan- or Pr(NO3)3-treated mice were less sensitive to phalloidin in vitro. These results indicate that the protective effect of these agents against phalloidin-induced hepatotoxicity may be mediated by their mitogenic properties.

Animals↗
PubMed1987

Large unilamellar liposomes with low uptake into the reticuloendothelial system.

Particulate drug carriers, including liposomes, are rapidly removed from blood by cells of the reticuloendothelial system (RES) with resulting adverse effects on this important host defense system. In order to overcome this and other major disadvantages of liposomes, we have altered liposome composition in an effort to achieve prolonged circulation half-lives. Gangliosides and sphingomyelin act synergistically to dramatically diminish the rate and extent of uptake of liposomes by macrophages in vivo. The significantly extended circulation times achieved by these modified large unilamellar liposomes overcome an important barrier to the targeting of particulate drug carriers to specific tissues in vivo.

Cholesterol↗
PubMedDate not supplied

The effect of acute alcohol ingestion on Fc-receptor-mediated clearance of IgG-tagged erythrocytes by the reticuloendothelial system in humans.

To help elucidate the pathogenesis of bacterial infections in alcoholics we documented reticuloendothelial system (RES) function in 14 healthy adults (9 males, 5 females, age: 22 +/- 2.6 years) prior to and following acute alcohol intoxication. Autologous erythrocytes were labelled with Cr51 isotope, tagged with anti-Rh IgG antibody, and infused into the systemic circulation. Blood samples were drawn at specific time intervals over a 2-h period and the radioactivity in each sample was used to develop computer-generated clearance curves from which half-lives (T1/2) were derived. Each study was carried out in the same individual on two separate occasions at least two weeks apart, once when sober and again one hour after ingestion of an intoxicating amount of alcohol (1 gm/kg over 1 h). Eleven of 14 participants showed no appreciable change in RES clearance capacity following alcohol ingestion. In the remaining three individuals alcohol prolonged the T1/2 by 38%, 38%, and 74% from when sober. These individuals were similar to other participants in terms of age, blood alcohol levels, pre- and postalcohol liver biochemistry, and hematologic and immunologic findings. Two of the three were HLA Dr5 positive, as compared to none of the 11 with unimpaired clearances. The results of this study suggest that perhaps a small subset of the population exists in whom acute alcohol intoxication impairs Fc-receptor-mediated RES clearance of IgG-tagged erythrocytes from the systemic circulation. This depression of RES function could contribute to the increased frequency and severity of bacterial infections reported in some alcoholics.

Adult↗
PubMedDate not supplied

Dynamic change of reticuloendothelial system function after surgical stress.

The influence of surgical stress on the function of the reticuloendothelial system (RES) is not well elucidated. Because we established an in vivo functional test for the RES by using chondroitin sulfate iron colloid in rabbits, the normal range of RES function in healthy volunteers (n = 12) and the dynamic change of RES function in surgical patients after distal gastrectomy (n = 14) were examined by this method. In healthy volunteers, the maximum phagocytic velocity and membrane-particle constant were 0.0310 +/- 0.0052 mg/kg per minute and 0.575 +/- 0.205 mg/kg, respectively. In surgical patients, maximum phagocytic velocity (postoperative day 1, 0.0408 +/- 0.0088; postoperative day 3, 0.0486 +/- 0.0115; and postoperative day 7, 0.0430 +/- 0.0115 mg/kg per minute) and membrane-particle constant (postoperative day 3, 0.717 +/- 0.169 mg/kg) significantly increased postoperatively in comparison with preoperative values. These results indicate that the total capacity of the RES is augmented but that its functional phagocytic efficiency is diminished after abdominal surgery. This phenomenon is considered to be one of the immunological alterations caused by surgical stress. The chondroitin sulfate iron colloid test can be applied to monitor the dynamic change of the RES function under various conditions.

Adult↗
PubMed1985

Function of reticuloendothelial system on CCl4 induced liver injury in mice.

Phagocytic activity as a function of the reticuloendothelial system (RES) has been studied in CCl4-induced liver injury by using the carbon clearance test. Liver damage in mice was induced by administration of 20% CCl4 in olive oil (p.o.). After a single administration of CCl4, significant increases in liver/body weight ratio, serum GOT and GPT levels, alpha, beta and gamma-globulins and BSP retention, and decreases in serum albumin, an activity of the hepaplastintest and the correct phagocytic activity, alpha value, were found. After 15 administrations of CCl4 (3 times a week), mild increases in serum GPT level and BSP retention and decreases in the activity of the hepaplastintest and both phagocytic indices, K and alpha values, were observed. However, zymosan treatment 3 days before sacrifice induced an increase in K value depressed by multiple administrations of CCl4. The depression of carbon uptake by Kupffer cells can be seen by light microscopy after multiple administrations of CCl4 compared with that of saline and olive oil. These findings indicate that the RES phagocytosis is suppressed more strongly in chronic liver injury by 15 CCl4 administrations than in acute injury by a single one, although the biochemical parameters indicating liver injury are shown to have an opposite tendency. A clear correlation between the alteration of RES activity and the degree of liver injury was not noted.

Alanine Transaminase↗
PubMed1987

Function of reticuloendothelial system on ethionine induced liver injury in mice.

Phagocytic activity as a function of the reticuloendothelial system (RES) has been studied in ethionine induced liver injury by using the carbon clearance test. Liver damage in male and female mice was induced by DL- and L-ethionine injections (1000 mg/kg/day, i.p.). In both female and male mice, a single dose or three injections of DL- or L-ethionine caused increases in liver/body weight ratio, A/G ratio, GOT and GPT levels, and BSP retention. There was the decrease of the total protein levels in the serum. The degree of liver injury was more severe after three injections of DL- and L-ethionine than after a single injection of them. After a single injection of ethionine, the L-isomer induced a slightly greater response than the racemic mixture, except for BSP retention. On the other hand, phagocytic activities by the carbon clearance test were increased after a single injection or three injections of DL- and L-ethionine. That is, the K value was increased in all ethionine treated mice except for females with three injections of DL-ethionine. The alpha value was increased after three injections in DL- and L-ethionine treated males and DL-ethionine treated females. In addition, the increase in carbon uptake by Kupffer cells can be seen by light microscopy after a single injection or three injections of DL- or L-ethionine. These findings indicate that ethionine injections induce the enhancement of RES phagocytosis, although the biochemical parameters indicating liver injury are changed severely. These results support the data indicating no correlation between the alteration of RES activity and the degree of liver injury.

Alanine Transaminase↗
PubMed1987

Role of the reticuloendothelial system in the catabolism of low density lipoprotein in the rat.

The role of the reticuloendothelial system (RES) in receptor-independent catabolism of human low density lipoprotein (h-LDL) was evaluated in the rat in vivo after blockade of its phagocytic activity with gadolinium chloride (GaCl3). After blockade of the RES with GaCl3, the recovery of [125I] h-LDL in the liver of 17 alpha-ethinyl oestradiol-treated rats (EE-rats), was decreased by 37 and 16%, 15 and 60 min after h-LDL injection, respectively. This decrease did not result in a decreased LDL degradation which represented 14 and 55% of the injected dose in the two groups of rats after 15 and 60 min respectively, both on GaCl3 and control rats. Contrasting with EE-rats, the catabolism of h-LDL in untreated rats is much slower and takes place essentially through a receptor-independent mechanism. Six hours after the injection of [125I] h-LDL, 64% of the dose was degraded. This proportion decreased to 45% after blockade of the RES phagocytic activity. This 30 percent difference represents the proportion of h-LDL catabolized by receptor-independent mechanisms present in the Küpffer and endothelial cells. We conclude from our study that in the normal rat, the parenchymal cells of the liver on the one hand and the Küpffer and endothelial cells on the other hand contribute 70 and 30% respectively to the receptor-independent catabolism of low density lipoproteins in vivo.

Animals↗
PubMed1991

[Experimental study of endotoxemia and reticuloendothelial system in hepatectomized cirrhotic rats].

UNLABELLED: To investigate acute hepatic failure associated with endotoxemia and reticuloendothelial system (RES) in hepatectomized cirrhotic patients, lipopolysaccharide (LPS) at the dose of 0.2 micrograms/100gBW was injected intravenously into the 70% hepatectomized three groups of rats as follows; LC: rats with thioacetamide-induced liver cirrhosis, CONTROL: rats with normal liver, LC + FN: cirrhotic rats with intravenous supplementation of fibronectin. 1) The survival rates at 24 hours after hepatectomy of each group of LC, CONTROL and LC + FN were 0%, 100%, and 80%, respectively. Residual liver of group-LC revealed massive necrosis in histological study. 2) Phagocytic index (K) of injected 3H-labeled LPS were 0.100/min, 0.155/min and 0.146/min, respectively. 3) Uptake of injected 3H-labeled LPS at 15 minutes after injection was remarkably elevated into the liver compared with the lung and spleen in each group. Also uptakes into the liver per gram of tissue were 0.96% ID/g, 3.00% ID/g and 1.46% ID/g, respectively, and those per total organ were 5.95% ID/TO, 8.20% ID/TO and 9.21% ID/TO, respectively. 4) Level of plasma fibronectin decreased and that of serum total bile acid increased remarkably after injection of LPS in group-LC compared with the others. These results suggest the mortality of hepatic necrosis by LPS in group-LC is attributed to markedly reduced RES function especially in the liver, and supplementation of fibronectin decreases the mortality by enhancing RES function.

Animals↗
PubMed1987

Reticuloendothelial system Fc receptor function in systemic lupus erythematosus: effect of decreased sensitization on clearance of autologous erythrocytes.

Recent reports of reticuloendothelial system Fc receptor function using anti-Rh(D) coated red blood cells (RBC) provide conflicting data regarding the degree of abnormality in systemic lupus erythematosus (SLE). The effect of different sensitizing doses of anti-Rh(D) on Fc receptor function was evaluated in 10 controls and 9 patients with SLE (5 with renal disease, 4 without) using 1 microgram anti-Rh(D) (6,700 molecules anti-Rh(D)/RBC by saturation analysis) and 0.125 microgram anti-Rh(D) (1,100 molecules/RBC). At the lower sensitizing dose the sensitivity of the assay was significantly increased. To correctly interpret the significance of studies of Fc receptor function from different centers, it is necessary to know the exact sensitizing doses used for each study.

Adult↗
PubMed1985

Defective reticuloendothelial system C3b mediated clearance in rheumatoid arthritis and vasculitis.

C3b receptor mediated clearance by the reticuloendothelial system (RES) was tested in vivo using autologous C3b coated, technetium labelled erythrocytes in patients with rheumatoid arthritis (RA) and rheumatoid vasculitis. Diminished C3b mediated erythrocyte clearance was found in all patients with rheumatoid vasculitis and some patients with active RA. Normal C3b mediated clearance was found in some patients with previous vasculitis, in remission when tested. These results are consistent with the hypothesis that acquired dysfunction of RES C3b receptors is implicated in the pathogenesis of rheumatoid vasculitis.

Adolescent↗
PubMed1979

Depression of the reticuloendothelial system following graded isoproterenol-induced myocardial injury.

The effect of experimental myocardial injury on reticuloendothelial system (RES) phagocytic function was investigated. Graded myocardial injury was produced in rats by the subcutaneous injection of isoproterenol in doses of 5, 50 or 500 mg/kg. Phagocytic index, determined from the clearance rate of gelatinized lipid emulsion at six hours after isoproterenol injection, showed a progressive depression with increasing severity of myocardial injury. The depression in phagocytic index was due primarily to a depression of hepatic phagocytosis. RES blockade induced with colloidal carbon prior to isoproterenol injection (650 mg/kg) increased the mortality rate from 20% to 87%. It was concluded that the depression of RES function during this form of myocardial injury may hasten the deterioration of the organism and that it may be important to consider the role of RES function during clinical cardiogenic shock.

Animals↗
PubMed1981

Cytomorphology and lysosomal enzyme activity of the haemopoietic and reticuloendothelial system of the SJL/J mouse.

The cytomorphology and lysosomal enzyme activity of the haemopoietic and reticuloendothelial system (RES) of SJL/J mice, which develop a spontaneous reticulum cell neoplasm type B (RCN-B), were studied. The cytological findings during development of the disease were a predominance of medium-sized lymphocytes and an increase in the number of hyperbasophilic cells and plasma cells in the RES. These pathological findings were compared to the changes due to ageing in control groups of healthy C3H/eB mice. Acid phosphatase activity increased in the RES, whereas that of beta-D-glucuronidase remained unchanged during development of the disease. These findings indicate that the RCN-B of the SJL/J mice bear a certain resemblance to Hodgkin disease in man.

Acid Phosphatase↗