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The information available concerning the effects of compounds utilized as pesticides on functions of the reticuloendothelial system is quite limited. Review of selected examples of such studies in this and other reports (3) reveals considerable diversity in terms of species of experimental animal, purity and dose of pesticide, length of exposure, and class of pesticide employed. Observations include depression, enhancement, or no significant effect on the selected reticuloendothelial system function studies. With the present available information it is difficult to formulate general conclusions or to predict whether or not any individual pesticide will consistently and significantly alter any specific function of the reticuloendothelial system. At the present time, it is not known if pesticides within a single chemical class act in a similar manner in regard to their ability to influence reticuloendothelial system function. In addition, the relationship, if any, between the toxic, mutagenic teratogenic, or carcinogenic potential of any pesticide and its ability to alter the reticuloendothelial system is also unknown. More extensive systematic studies in experimental animal models would appear to be required before protocols to effectively evaluate the potential of pesticides to influence reticuloendothelial system function in man can be developed.
Reticuloendothelial System (RES) Fc receptor-mediated immune clearance and levels of immune complexes were measured in patients with systemic lupus erythematosus undergoing plasmapheresis. RES clearance defects improved and disease manifestations and levels of circulating immune complexes decreased after plasmapheresis. Patients with initially abnormal reticuloendothelial system function, elevated levels of circulating immune complexes, and active acute illness appeared to respond to plasmapheresis. One patient with normal immune clearance, lacking measureable immune complexes, and manifesting chronic disease remained unchanged. Improvements seen following plasmapheresis were best maintained in patients receiving parenteral cyclophosphamide in the post-pheresis period. The correlation of clinical response, improved RES function, and decreased levels of immune complexes suggests the interaction of the latter two parameters in disease pathogenesis. Plasmapheresis has an important role as a research tool, and may be of clinical usefulness in a small number of patients with serious complications of systemic lupus erythematosus.
The reticuloendothelial system (RES) is part of the host defence and consequently plays an important role in shock and trauma, conditions often requiring volume replacement. Experimental studies have shown that the functions of the RES are hampered by plasma substitutes such as gelatin, starch and dextran. In this study six patients undergoing elective cholecystectomy were given 500 ml dextran just before the operation. At the end of the operation the phagocytic and metabolic functions were tested with microaggregated human serum albumin labelled with I125. The results indicate that there is a significant impairment of the phagocytic activitity of the RES in patients given dextran compared to controls not given dextran but saline. The metabolic activity was not significantly affected by dextran, however, suggesting that moderate dosage of dextran is not of great disadvantage to patients undergoing major surgery.
The reticuloendothelial system of mice bearing EMT6 tumors was effectively blocked by intravenous injections of small unilamellar vesicles that incorporated a 6-aminomannose derivative of cholesterol in the lipid bilayer. Neutral liposomes loaded with indium-111-nitrilotriacetic acid were then injected. Fifty percent more radioactivity was deposited in tumors of the animals with blocked reticuloendothelial systems than in controls. Twenty-four hours after the injection of radioactive vesicles, well-defined tumor images were observed in whole-body gamma camera scintigraphs. Biodistribution studies showed that tumors from animals with blocked reticuloendothelial systems had more than twice the radioactivity per gram than any other tissue analyzed.
Physiologically, the main function of alpha 2-macroglobulin is the binding of active endopeptidases rather than their inhibition. The interaction results in a conformational change in the alpha 2-macroglobulin that leads to its rapid elimination by the reticuloendothelial system. In this way, the reticuloendothelial system may help in the regulation of extracellular proteolytic activity resulting from the release of proteinases from injured pancreatic acinar cells in acute pancreatitis. To evaluate this concept, the effect of feeding a choline-deficient diet supplemented with 0.5% DL-ethionine was determined in 4 and 6-wk-old mice in which the reticuloendothelial system was normal, stimulated, or depressed. Stimulating the reticuloendothelial system in 4-wk-old mice significantly (a) decreased the mortality rate; (b) lessened the drop in the plasma content of both alpha 2-macroglobulin and alpha 1-antitrypsin; and (c) decreased the severity of pancreatitis noted microscopically. In contrast, reticuloendothelial suppression in this group of mice had no demonstrable effect. However, when similar studies were done in 6-wk-old mice, in which this diet induces a milder disease, reticuloendothelial suppression significantly increased the mortality rate as compared with normal mice, whereas reticuloendothelial stimulation significantly decreased it. The possible mechanism for the salutory effect of stimulating the reticuloendothelial system on the outcome of diet-induced pancreatitis in mice is discussed.
HYPOTHESIS: Reticuloendothelial system function is altered in patients with multiple trauma and organ failure. DESIGN: Prospective cohort study. SETTING: Surgical intensive care unit at a level I trauma center. PATIENTS: Patients with multiple blunt trauma and injury severity scores greater than 20, with no referrals. INTERVENTIONS: Every second day reticuloendothelial system (RES) clearance capacity and liver blood flow were determined by administering labeled human albumin. Liver function was measured by enzymatic decay of indocyanine green, and levels of plasma tumor necrosis factor alpha were evaluated. RESULTS: In nonsurviving patients with blunt trauma, RES function was altered and was associated with organ dysfunction and infectious complications. Of 61 patients, 42 survived and 19 did not. Sixteen patients (84%) died of multiple organ failure. Significantly elevated RES activity (colloid clearance rate) was present between day 5 and day 13 after trauma in nonsurvivors (0.86+/-0.16 [mean +/- SD] on day 7, P = .003) compared with survivors (0.48+/-0.08 on day 7) and 20 healthy volunteers (0.47+/-0.06); RES activity then decreased to subnormal levels in nonsurvivors. Tumor necrosis factor alpha plasma levels were elevated early after injury only in nonsurvivors (on day 1: nonsurvivors, 1.2+/-0.4 ng/mL [mean +/- SD]; survivors, 0.5+/-0.2 ng/mL; P = .02). Indocyanine green half-life values increased late after trauma, indicating late organ failure (on day 19: nonsurvivors, 111+/-29 minutes [mean +/- SD]; survivors, 12+/-4 minutes; P<.001). CONCLUSIONS: Early after trauma, nonsurviving patients demonstrated increased proinflammatory cytokine levels, followed by a state of pathological hyperactivation of the reticuloendothelial system prior to death. These results indicate that the stationary host defense system is involved in the mechanisms causing organ failure after severe trauma.
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.
We have studied the selectivity of the murine reticuloendothelial system in recognizing and removing from the blood model immune complexes and several aggregated proteins. Although both IgG anti-DNP model immune complexes and micro-aggregated albumin exhibited rapid hepatic uptake, which is saturable, they did not cross-inhibit each other. Aggregates of ovalbumin, a glycoprotein rich in mannose (a sugar recognized by Kupffer cells), had no effect on the uptake by the liver of either IgG immune complexes or micro-aggregated albumin. The finding that transferrin aggregates were not taken up by the liver at all suggests that aggregation alone is not sufficient to overcome the lack of a specific hepatic receptor for that protein. Thus, several mechanisms exist whereby aggregated proteins can be cleared from the blood by the reticuloendothelial system, an observation consistent with the selective failure of reticuloendothelial function found in several human diseases.
This study examines the role of the reticuloendothelial system in the metabolism and tissue uptake of chemically modified human low density lipoprotein (LDL) in rabbits. Treatment with 1,2-cyclohexanedione or HCHO/NaBH4 abolishes receptor-mediated catabolism of the lipoprotein and restricts its clearance to receptor-independent pathways. When the plasma clearances of the two modified lipoproteins were measured in rabbits the 1,2-cyclohexanedione-treated LDL was removed 19% faster (P less than 0.001) than HCHO/NaBH4-treated LDL. This was associated with an increased uptake of 1,2-cyclohexanedione-treated LDL over HCHO/NaBH4-treated LDL into tissues, particularly the liver and spleen, suggesting that their differential clearance may have involved the reticuloendothelial system. To examine this possibility the experiment was repeated in animals whose reticuloendothelial activity had been suppressed by injections of an ethyl oleate emulsion. This reduced the difference in the plasma clearance rates of 1,2-cyclohexanedione-treated LDL and HCHO/NaBH4-treated LDL and virtually abolished their differential tissue uptakes, adding weight to the proposal that the reticuloendothelial system may be involved in the receptor-independent catabolism of LDL.
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The reticuloendothelial system function, especially phagocytic activity, and hepatocyte function were investigated in dogs undergoing an orthotopic liver transplantation. The donor's phagocytic index, measured by a lipid emulsion test, was higher in the Survivor group which survived more than 3 days after transplantation (0.063 +/- 0.008 vs 0.024 +/- 0.002; mean +/- standard error of the mean (SEM), P < 0.01). There was a statistically significant difference in the phagocytic index between the survivor and nonsurvivor groups. However, the hepatocyte function at an early phase after transplantation, indicated by the arterial ketone body ratio, hepaplastin test and lecithin cholesterol acyltransferase level, did not distinguish the Survivor group from the Nonsurvivor group at all. In the survivor group, the hepaplastin test and the lecithin cholesterol acyltransferase level were significantly decreased after liver transplantation, namely from 155 +/- 15% to 58 +/- 5% and from 57 +/- 12 unit/ml to 19 +/- 1 unit/ml on the 2nd day after transplantation (P < 0.01, P < 0.05), respectively. On the other hand, the reticuloendothelial system (RES) function, as estimated by the phagocytic index and serum complement activity (CH 50), demonstrated no change throughout the experimental period. The present study therefore demonstrated that the operative results might be affected by the phagocytic activity.
The purpose of this study was evaluation of the phagocytic ability of peripheral blood leucocytes and reticuloendothelial system of the lungs, liver and spleen after one infusion of plasma-substituting preparations: Fluigel and dextran 70 in volumes of 20 ml/kg of body weight. The experiments were done in rabbits. The response of the reticuloendothelial system was assessed on the basis of its ability of eliminating foreign erythrocytes labelled with 51Cr from the circulating blood and radioactivity accumulation in the liver and spleen. It was found that infusion of Fluigel and dextran produced transient changes in the function of the reticuloendothelial system with increased number of granulocytes and a fall of their radioactivity 3 and 6 hours after infusion, reduced ability of pulmonary 51Cr accumulation and increased storage in the spleen observed 24 hours after infusion.
To evaluate the function of the reticuloendothelial system and macrophage-monocyte system, blood samples from Thorotrast patients and age-matched healthy controls were used to determine the titer of plasma antibodies to lipid A and the numbers of several lymphocyte subclasses in peripheral blood and for an autoradiographic study of peripheral blood monocytes. The titer of plasma IgM class antibodies to lipid A was significantly elevated in the Thorotrast patients. Counts of CD 11-positive lymphocytes and CD 57-positive lymphocytes, which correspond to monocytes and natural killer cells, respectively, were significantly increased in the Thorotrast patients. Autoradiography showed that alpha-particle tracks were emitted from the monocytes isolated from the peripheral blood of Thorotrast patients. Thus the depressed function of the reticuloendothelial system resulted in the activation of the macrophage-monocyte system in the Thorotrast patients.
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