Studies of the Reticuloendothelial System (RES). III. Blockade of the RES in Man *

Abstract

In a previous communication (1), we have presented data indicating that the phagocytic capacity of the reticuloendotheial system (RES) in man can be determined safely and effectively by measuring the rate of disappearance of various doses of radioisotopically labeled aggregated human serum albumin particles from the blood after intravenous injection. Subsequently we reported that in patients with pneumococcal pneumonia, typhoid fever, and pneumonic tularemia (2), the phagocytic capacity of the RES was increased as evidenced by an accelerated rate of clearance of the aggregated albumin (AA) from the blood. In contast, in both viral infections studied, dengue and sandfly fever (3), there was a temporary inhibition of the body's ability to clear aggregated albumin, a finding consistent with studies in experimental animals in which phagocytic ability was found to be inhibited by viral infections (4). The safety of the method has been further confirmed during studies of the relationship between RES phagocytic activity in man and endotoxin tolerance (5). To date, over 1,500 administrations have been made in over 300 individuals without untoward reactions of any type. Therefore, we extended the studies in an attempt to characterize in man the phenomenon of RES blockade, the latter being defined as retardation of the usual rate at which particulate matter is removed from the circulation (6).In the present study, we have utilized in man and dog a modification of the technique employed by Murray in studies of rats (7). The RES was blockaded by administering various types of particles, and the effectiveness of blockade was tested by the subsequent injection of tracer doses of similar or dissimilar particles.* Submitted for publication August 13, 1963; accepted March 19, 1964. t U. S. Public Health Service trainee, National Institutes of Health grant H-6454.In this report we will demonstrate that blockade of the RES in man as in experimental animals is relatively specific for the type of particle. Such specificity is not complete in that a significant depression of the clearance of dissimilar particles is noted, although to a far less degree than the depression of clearance of similar particles. MethodsThe particles used to produce blockade of the RES were AA prepared by the method described in a previous paper (1)

Improved Tumor Uptake by Optimizing Liposome Based RES Blockade Strategy

“…It has also been reported that the same strategy worked for iron oxide nanoparticles 23 or carbon 29, evidenced by qualitative or semi-quantitative comparison. Meanwhile, several authors reported that they did not observe RES depression following a primary dose of colloid during a secondary dose of different colloid 38. They attributed this to the fact that opsonization of the first material did not necessarily cause RES depression of the second material.…”

Red cell survival studies in hereditary spherocytosis

“…The phenomenon of reticuloendothelial blockade has been known for years and describes the depressed rate of clearance of a tracer dose of colloid after intravenous injection of a large blockading dose of colloid. This blockade is often quite specific and will only operate when the test material has the same surface characteristics as the blockading agent (19)(20)(21). Moreover in some studies retiGuloendothelial blockade seemed to be dependent on the persistence in the circulation of the original blockading dose of colloid (20,22).…”

Mechanisms of Endotoxin Tolerance

“…Thorotrast administered either 3.5 hours or immediately before the start of a continuous intravenous infusion of endotoxin failed to enhance appreciably the febrile response, in contrast to its effect when the same quantities of endotoxin were administered as a single intravenous injection. It may be recalled that RES blockade with any agent is rarely complete and is best demonstrated by rapid injection of a large test bolus of particles (41,42). Consequently, administration of a given quantity of colloid as a slow continuous intravenous infusion would not be expected to impose the same stress on a blockaded RES as would sudden injection of the entire bolus.…”