Phagocytic Activity Of Reticuloendothelial System Research Articles

Polymeric protective agents for nanoparticles in drug delivery and targeting

Surface modification/functionalization of nanoparticles (NPs) using polymeric protective agents is an issue of great importance and actuality for drug delivery and targeting. Improving the blood circulation half-life of surface-protected nanocarriers is closely related to the elimination of main biological barriers and limiting factors (protein absorption and opsonization), due to the phagocytic activity of reticuloendothelial system. For passive or active targeted delivery, in biomedical area, surface-functionalized NPs with tissue-recognition ligands were designed and optimized as a result of modern research techniques. Also, multi-functionalized nanostructures are characterized by enhanced bioavailability, efficacy, targeted localization, active cellular uptake, and low side effects. Surface-protected NPs are obtained from biocompatible, biodegradable and less toxic natural polymers (dextran, β-cyclodextrin, chitosan, hyaluronic acid, heparin, gelatin) or synthetic polymers, such as poly(lactic acid), poly(lactic-co-glycolic) acid, poly(ε-caprolactone) and poly(alkyl cyanoacrylates). PEGylation is one of the most important functionalization methods providing steric stabilization, long circulating and ‘stealth’ properties for both polymeric and inorganic-based nanosystems. In addition, for their antimicrobial, antiviral and antitumor effects, cutting-edge researches in the field of pharmaceutical nanobiotechnology highlighted the importance of noble metal (platinum, gold, silver) NPs decorated with biopolymers.

The splenic toxicity of water soluble multi-walled carbon nanotubes in mice

Spleen is an important immune organ and a constituting part of the reticuloendothelial system (RES). CNTs in vivo can be readily scavenged from blood and mainly entrapped by liver, spleen and lungs. Herein, water soluble multi-walled carbon nanotubes (S-MWCNTs) were used as a model to investigate the possible toxicity of carbon nanotubes (CNTs) to mouse spleen. The toxicity of various doses of S-MWCNTs was examined by carbon clearance measurement, oxidative stress assay, histopathologic and electron-microscopic examination. Compared with the control group, phagocytic activity of RES, activity of reduced glutathione, superoxide dismutase and malondialdehyde in splenic homogenate did not change significantly in 2 months. The histopathologic examination showed no observable sign of damage in spleen; however, the accumulated S-MWCNTs gradually transferred from the red pulp to the white pulp over the exposure time and might initiate the adaptive immune response of spleen.

Spontaneous bacterial peritonitis: a historical perspective: Kerr DNS, Pearson DT, Read AE. Infection of ascitic fluid in patients with hepatic cirrhosis [Gut 1963; 4: 394–398]; Conn HO. Spontaneous peritonitis and bacteremia in Laennec's cirrhosis caused by enteric organisms. A relatively common but rarely recognized syndrome [Ann Intern Med 1964; 60: 568–580

Spontaneous bacterial peritonitis: a historical perspective: Kerr DNS, Pearson DT, Read AE. Infection of ascitic fluid in patients with hepatic cirrhosis [Gut 1963; 4: 394–398]; Conn HO. Spontaneous peritonitis and bacteremia in Laennec's cirrhosis caused by enteric organisms. A relatively common but rarely recognized syndrome [Ann Intern Med 1964; 60: 568–580

Experimental studies of the value of SPIO for MRI of bone marrow before and after whole body irradiation

Evaluation of the value of superparamagnetic iron oxides (SPIO; Endorem) for MRI-derived quantifications of the permeability of the blood-bone marrow barrier and the phagocytic activity of reticuloendothelial system (RES) bone marrow cells before and after TBI. 12 New Zealand white rabbits underwent MRI of the lumbar spine and os sacrum using T1-weighted spinecho (SE) and T2-weighted Turbo-SE (TSE) sequences before and after injection of SPIO (Endorem). Four animals each were examined without irradiation, after 4 Gy total body irradiation (TBI), and after 12 Gy TBI. Changes in bone marrow signal intensities (SI) after contrast agent injection were quantified as delta SI(%) = SIpost-SIpre)/SIpre) x 100% and these data were correlated with bone marrow histopathology. Histopathology of the bone marrow revealed a radiation-induced decline of all hematopoetic cell lines. SPIO were phagocytosed by bone marrow RES cells and caused a significant bone marrow signal decline on postcontrast T2-weighted images (p < 0.05). delta SI(%) data for T2-weighted images were significantly higher for the irradiated bone marrow as compared to non-irradiated controls (p < 0.05). Dynamic T1-weighted images directly after contrast medium injection were not able to characterize the permeability of the blood-bone marrow barrier. Hematopoetic bone marrow can be labelled with SPIO. Irradiation does not impair the phagocytic activity of bone marrow RES cells. However, the bone marrow enhancement with SPIO is smaller as compared to previous results obtained by our group with USPIO.

The immuno-stimulant OK-432 enhances liver regeneration after 70% hepatectomy

The effect of reticuloendothelial system activation on hepatic regeneration after 70% hepatectomy was investigated. OK-432, a killed streptococcal preparation which increases reticuloendothelial system function, was administered to rats prior to 70% hepatectomy. Hepatic incorporation of 3H-thymidine 24 h after 70% hepatectomy was enhanced by OK-432 pretreatment. DNA synthesis was greater in pretreated than in control rats and correlated highly with reticuloendothelial system phagocytic activity prior to surgery. Methyl palmitate, which decreases reticuloendoethelial system function, was administered to rats prior to 70% hepatectemy. Hepatic incorporation of 3H-thymidine 24 h after 70% hepatoctomy was significantly depressed by methylpalmitate-pretreatment. These data suggest that reticuloendothelial system palys a role in liver regeneration and that hepatocyte proliferation might be enhanced by protection from surgical stress and endotoxins with reticuloendothelial system stimulation by OK-432.

Effect of chronic interleukin-2 treatment on RES phagocytic activity in the rat

The effect of chronic interleukin-2 (IL-2) injection upon reticuloendothelial system (RES) function in the rat has been determined. Seven-day treatments with two doses of human recombinant IL-2 resulted in a dramatic reduction in the phagocytic uptake of the liver and spleen, while increasing the weight of both organs. There were dramatic histological changes in the intestine, liver and spleen as well. These results suggest that the chronic use of IL-2 can result in hepatic dysfunction, which is associated with altered RES phagocytic function.

Effect of soft x-ray irradiation on immunological functions in mice.

Effect of soft x-ray irradiation on immunological functions in mice was investigated. Soft x-ray irradiation with 100R or more induced a significant reduction in the number of plaque-forming cells (PFC). The reduction in the number of PFC depended on the irradiation doses. Irradiation with 600R or more showed a significant reduction in the delayed reaction of footpad swelling. However, soft x-ray irradiation with doses ranging from 100R to 1000R did not exert significant influence on the K values of carbon clearance test. Irradiation with 100R or more of soft x-ray showed a remarkable reduction of response to concanavalinA (ConA) or lipopolysaccharide (LPS) in spleen cells, and the response to ConA was lower than that to LPS. These results suggest that in the soft x-ray-irradiated mice, antibody-producing ability, delayed type hypersensitivity reaction and mitogenic activity are sensitive to soft x-ray irradiation and furthermore, T cell is more sensitive than B cell, but phagocytic activity of reticulo-endothelial system (RES) is resistant to soft x-ray irradiation.

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.

Prevention of Galactosamine-Induced Hepatotoxicity in Rats with Fructose-16-Diphosphate

Galactosamine (GalN) administration produces hepatitis-like liver injury in animals. The hepatotoxicity of GalN is attenuated by several interventions, including activation of the reticuloendothelial system (RES). Fructose-1,6-diphosphate (FDP) administration significantly increases the phagocytic activity of the RES in animals. Thus, investigations were designed to determine whether FDP affords protection against GalN toxicity. Rats were injected with GalN (375 mg/kg) and treated with 0.9% NaCl (n = 8) or FDP (n = 9). Eight rats were sham-operated. Serum glutamic oxaloacetic transaminase was 40 times higher in the saline group as compared to the FDP-treated rats (p less than 0.0001). Glutamic pyruvic transaminase, gamma-glutamyltranspeptidase and bilirubin were similarly elevated (saline vs. FDP, p less than 0.005, p less than 0.01 and p less than 0.05, respectively). These values were not different between FDP-treated and sham-operated rats. Extensive hepatic necrosis was observed in all saline-treated rats, whereas in the FDP group only isolated foci of hepatocellular necrosis were noted. The hepatoprotective effect of FDP in this model is attributed to its ability to enhance the phagocytic activity of RES and to suppress release of oxyradicals by the leukocytes during the inflammatory phase.

Study on antitumor and immunomodulating activities of polysaccharide fractions fromPanax ginseng: Comparison of effects of neutral and acidic polysaccharide fraction

The crude polysaccharide fromPanax ginseng prepared by hot water extraction and precipitation with ethanol was further fractionated into neutral and acidic fractions by DEAE-cellulose ion exchange chromatography. The chemical compositions were 85.0% carbohydrate and 15.0% protein for the neutral fraction, and 28.4% carbohydrate, 10.0% protein and 29.0% uronic acid for the acidic fraction. The acidic fraction was more effective in increasing of the ratio of spleen to body weight, the number of antibody secreting cells to SRBC and phagocytic activity of reticuloendothelial system, as well as antitumor activity against the solid form of sarcoma 180 in ICR mice than the neutral fraction. All polysaccharide fractions were mitogenic to cultured spleen cells of C57BL/6 mice. However, FA was different from FN in the co-mitogenicities with lectin mitogens. Both crude and acidic fractions potentiated remarkably the mitogenic activity of PHA-P or LPS in dose-dependent manner but neutral fraction enhanced only that of LPS. Three polysaccharide fractoins had no effect on that of Con A. These results suggest that the acidic fraction may stimulate B and T cells as well as macrophages while the neutral fraction may stimulate only B cells and macropages.

Effect of acute burn trauma on reticuloendothelial system phagocytic activity in rats. II: comparison of uptake of radiolabelled colloid and bacteria

The uptake of radiolabelled colloid or bacteria was compared in normal rats and animals subjected to acute burn trauma. The uptake of colloid by the liver was unaffected by burn trauma, but uptake of the labelled bacteria was reduced. Spleen uptake of both colloid and bacteria was reduced by burn trauma while lung uptake was increased. These data are consistent with the hypothesis that acute burn trauma alters reticuloendothelial system phagocytic activity in the rat towards both inert particles and live bacteria.

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.

マウス網内系の貪食能に及ぼす淫羊〓の影響

Effects of a 70% methanolic extract (E-S) from the dried leaves of Epimedium sagittatum on a phagocytic activity of reticuloendothelial system were studied by the carbon clearance method in mice. The clearance-rate of carbon significantly increased 1 h after the oral administration of E-S (200 or 500 mg/kg, one time/d for 5d). E-S activated the phagocytosis of carbon by Kupffer cells in the liver. Icariin and epimedin C isolated from E-S also activated the phagocytosis. These results suggest that E-S promotes the phagocytic activity of the reticuloendothelial system in mice and has a stimulatory effect on macrophage.

生薬・マムシの薬理活性研究(第2報)マウス網内系の貪食能に及ぼす50%エタノールエキスの影響

Effect of a 50% ethanolic extract ([M]) from dried whole body of Agkistrodon blomhoffii blomhoffii Boie on a phagocytic activity of reticuloendothelial system was studied by the carbon clearance method in mice. The clearance-rate of carbon was significantly shortened 1 h after the oral administration of [M] (250 or 500 mg/kg, one time/d for 3d). [M] activated the phagocytosis of carbon by macrophage (M phi) in the spleen and the phagocytosis of latex by peritoneal M phi. These results suggested that [M] may promote the phagocytic activity on the reticuloendothelial system in mice and has a stimulatory effect on M phi.

Effect of aflatoxin B1 on the delayed type hypersensitivity and phagocytic activity of reticuloendothelial system in chickens.

Efforts were made to see the effect of feeding aflatoxin B1 at 0.3 ppm level on various aspects of the immune system in chickens. The birds were fed aflatoxin B1 (AFB1) mixed ration from 0 to 6 weeks of age and thereafter normal feed was given up to 12 weeks of age. The delayed type hypersensitivity reaction of these birds was assessed by contact sensitivity to Dinitrofluorobenzene. The dietary AFB1 significantly suppressed the cell mediated immune response at all the three periods tested (30, 45 and 60 days of age). The toxin showed residual effect on immunity as the suppression of cell mediated immunity was maximum three days after the withdrawal of toxin from the feed. The effect of AFB1 on the phagocytic status of reticulo endothelial system (RES) was assessed by colloidal carbon clearance test at various intervals. The residual effect of toxin was observed on RES too as phagocytic index of AFB1 fed birds was significantly lowered up to 45 days of age.

The effects of ulinastatin on the reticuloendothelial system (RES) of rabbits in endotoxin shock.

Carbon clearance, concentration of fibronectin (Fn) in the blood and arterial ketone body ratio (AKBR) have been measured in the rabbit in order to evaluate the RES phagocytic activity and the effect of ulinastatin on it in endotoxin (ET) shock. The following results were obtained: 1) carbon deposition by ET injection was found in organs (lung and kidney) which did not show it in the control group. The reasons for this might be considered that the RES was blocked because of phagocytizing ET and tissue debris, so that the carbon which could not be processed by the RES spilled over and became clogged; 2) the RES phagocytic activity were found to decline from an early stage after injection of a lethal dose of ET due to a decline in Fn productivity and an increase in Fn consumption; and, 3) ulinastatin suppressed the decrease of Fn and the carbon deposition in the kidney in ET shock. These results are suggestive of the usefulness of ulinastatin as an anti-shock agent, preserving the RES phagocytic activity through the inhibition of Fn consumption.

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.

Reticuloendothelial system phagocytic activity in cirrhosis and its relation to bacterial infections and prognosis.

The reticuloendothelial system phagocytic activity, estimated by the plasma elimination rate constant of 99mtechnetium-sulfur colloid, was studied in 41 decompensated cirrhotics and 10 normal subjects. The results were related to the incidence and type of bacterial infections occurring during hospitalization and follow-up, and to survival. The elimination rate constant of 99mtechnetium-sulfur colloid was lower in cirrhotic patients (0.168 +/- 0.007) (means +/- S.E.) than in normal subjects (0.220 +/- 0.005) (p less than 0.01). Cirrhotics were divided into two groups. Group I (16 patients) and Group II (25 patients) had normal or reduced elimination rate constant of 99mtechnetium-sulfur colloid, respectively. Both groups were similar in relation to clinical and biochemical data, hepatic blood flow, and wedged hepatic venous pressure. However, the liver scan and the elimination rate constant of indocyanine green were more altered in Group II. Patients in Group II developed acute bacterial infections more frequently than did patients in Group I. During hospitalization (24 +/- 2 days), bacteremia occurred in six patients in Group II and in none in Group I (p less than 0.05). During follow-up (28 +/- 3 months), 5 patients in Group II and none in Group I developed bacteremia (p less than 0.05). The cumulative survival rate of Group I patients was higher (p less than 0.05) than that of Group II patients at 3 months (100 vs. 80%), 6 months (94 vs. 68%), 24 months (74 vs. 42%), and 48 months (68 vs. 34%). We suggest that decompensated cirrhotics with depressed reticuloendothelial system phagocytic activity are at great risk to acquire bacteremia, and that reticuloendothelial system phagocytic activity has prognostic value in cirrhosis.

Susceptibility of two colonies of Wistar rats to inflammation, with particular reference to delayed hypersensitivity.

Two colonies of Wistar rats were tested for their abilities to produce delayed hypersensitivity reactions and other forms of inflammation. Tuck rats, which respond to dextran with an anaphylactoid reaction, produced delayed reactions to tuberculin protein and to ovalbumin in Freund's incomplete adjuvant. On the other hand, NELP rats which do not respond to dextran also produced delayed reactions to tuberculin protein, but only to ovalbumin when this was contained in Freund's complete adjuvant. Rats of both colonies responded to cotton pellet-induced inflammation, but the adult NELP rats showed resistance both to adjuvant-induced and to collagen-induced arthritis, as well as to the production of experimental allergic encephalomyelitis. NELP rats also showed a much greater reticulo-endothelial system phagocytic activity although antibody titres to sheep red blood cells and the mitogenic activity of concanavalin A and of lipopolysaccharide on spleen cells were similar in the two colonies of rats.

Role of spleen in choline stimulation of reticuloendothelial system and resistance to acute hemorrhage.

SummaryExperiments were undertaken, with rats, to determine whether the spleen plays a role in choline chloride-induced reticuloendothelial system (RES) phagocytic stimulation and protection against circulatory shock. Choline pretreatment of normal, intact, but not splenectomized rats, resulted in heightened RES phagocytic stimulation and protection against acute hemorrhagic shock. Choline pretreatment significantly increased spleen size in normal intact rats. Wet liver or lung weights were not significantly affected by choline pretreatment of either normal or splenectomized rats. Untreated, splenectomized animals did not demonstrate any significant alterations in either RES phagocytic activity or RE organ wet weights when compared to normal, intact controls or to sham-operated animals. Although the results of these experiments make it clear that the presence of a functioning spleen is necessary for choline-induced RES stimulation and shock protection, it is not clear as to just how these actions are brou...