Blockade of the Reticuloendothelial System

BLOCKADE OF THE RETICULOENDOTHELIAL SYSTEM, a method of inactivating the functions of the latter by loading its cells with various substances that are usually deposited in them (various suspensions, colloidal metals, colloidal dyes, protein suspensions, and in particular, heterologous blood serum). The method of blockade was first used in studying the sites of formation of bile pigments in the body in connection with the question of the occurrence of hemolytic jaundice (Lepehne, Eppinger, and others). Subsequently, the blockade method was applied to clarify the significance of the reticuloendothelial system in lipid metabolism and in the process of antibody formation. Significant disagreements arose regarding whether it is actually possible to achieve blockade of the reticuloendothelial system, i.e., the destruction of its functions by loading the cells with the substances mentioned. To resolve this question, the method of saturating the reticuloendothelial system with two different substances introduced simultaneously was used. It was found that the ability of the reticuloendothelial system to bind various substances, even after blockade by others, is extremely great. There are even indications that this ability, with respect to another subsequently introduced substance, is manifested to an even greater degree as one substance is introduced (Kuczynski). Thus, instead of blockade, stimulation occurs. However, with local introduction of blocking substances (for example, lipoids) into tissues, it is still possible to achieve such complete loading of individual cells (histiocytes) that they subsequently lose the ability to take up vital stains (Kuznetsovsky). The impossibility of blocking the reticuloendothelial system as a whole is also proven by the study of blood in blocked animals. The absence of changes in blood during blockade speaks against its completeness (Rosier). The possibility of reducing the production of bile pigments by blockade (proposed mainly by Lepehne) is denied by many authors. Similarly, the data regarding the effect of blockade on cholesterol metabolism are contradictory. Thus, on the one hand, an increase in blood cholesterol content was observed after removal of part of the reticuloendothelial system and blockade of the reticuloendothelial system (Soper, Eppinger), on the other hand, the studies of Rosenthal, Moses, and Petschel gave no positive results in this respect. The phagocytic ability of the cells of the reticuloendothelial system (according to the data of Oeller, Seiffert, and Siegmund) not only does not decrease, but, on the contrary, increases. The ability to produce antibodies after blockade, according to some authors, decreases. In contrast to this, the production of agglutinins in blocked animals is even increased. In general, from all the currently extremely contradictory data regarding the significance of blockade, it must be accepted that weakening of the functions of the reticuloendothelial system by this method is achieved far from in all cases, if it is achievable at all. The species of animal used for experiments, the substance used for blockade, and the method of conducting the blockade itself are of great importance in this respect. The species of animal is important in that the phagocytic ability of the cells of the reticuloendothelial system is expressed to a significantly different degree in different species (Kraft). The nature of the substance taken for blockade is important, since some substances are deposited exclusively in the hepatosplenic system, while others are deposited throughout the reticuloendothelial system. There are also very large differences in the degree of deposition of various commonly used substances in different organs (Teplov, Kagan). The dosage of the introduced substance and the duration of its introduction are particularly important in blockade. With chronic introduction for the purpose of blockade of suspensions or colloidal substances, blockade cannot be achieved, because new regenerating elements of the reticuloendothelial system take the place of the blocked cells, the cells of which undergo hyperplasia during chronic blockade (Hesse). To achieve at least partial blockade of the reticuloendothelial system, it is necessary to introduce large amounts of blocking substances over a relatively short period, before the "activation" of the system due to the regenerative capacity of its cells has occurred. Thus, when loading the cells of the reticuloendothelial system, apparently a partial blockade of it first occurs, and then an increase in phagocytic ability (Leites), i.e., stimulation. Due to many authors not sufficiently taking into account these various phases of blockade, the lack of precise dosage of substances used for blockade, etc., many results obtained by the blockade method must be treated with great caution, all the more so that simultaneously with blockade of the reticuloendothelial system, loading with the introduced substances of other cells (for example, liver cells) also occurs, and it is also possible that the introduced substances are deposited outside the cells, for example, in the walls of blood vessels, which of course also does not remain without influence on tissue metabolism processes. Despite the fact that the concept of blockade of the reticuloendothelial system has not yet been fully defined, it must still be considered that this concept is quite real.

N. Anichkov. Blockade of the active elements of the physiological system of connective tissue is of great importance in clinical pathology. It has to be dealt with in infectious processes, in tumor growth (Bogomolets, Neiman, Roskin), it is a very unpleasant complication in heteroproteinotherapy, in anaphylaxis. N. N. Sirotinin showed that in anaphylactic shock, the decrease in adsorptive ability (blockade) of the reticuloendothelial system occurs regularly and usually many times exceeds the blockade observed with the introduction of colloidal suspensions. A cytotoxic (for connective tissue) serum was proposed (Bogomolets) as a blocking agent. Large doses of this serum sharply suppressed the production of agglutinins (Leontiev) and hemolysins (Varshamov), while small doses, on the contrary, sharply stimulated the formation of antibodies, allowing their content in the blood to be brought to extremely high levels. In application to cancer transplants (Bogomolets and Neiman) and to cancer explants (Kavetsky), large doses of serum that block connective tissue suppressed the resistance of the reticuloendothelium and promoted the in vivo growth and metastasis of cancer epithelium and enhanced its growth in vitro in tissue cultures. Conversely, small doses had a stimulating effect on active connective tissue, enhancing the formation of a demarcation line, limiting tumor growth, and often causing its resorption. Similar results were obtained by Neiman in mouse spirochetosis. The significance of these experiments for the problems of immunity and neoplasia is obvious. Blockade is a functional concept and can be extended to the action of various substances that suppress the adsorptive capacity of connective tissue. Such are, for example, certain substances of professional importance - lead, arsenic (Kavetsky). Here also the principle holds that if large doses cause blockade, then small doses of the same substance, on the contrary, stimulate. This is also the basis for attempts to use colloidal metals (silver, gold, lead) and protein therapy in infections and in cancer. The degree of blockade of the reticuloendothelial system can be determined by various methods: 1) studying under a microscope the uptake of coarse-dispersed dye introduced after blockade by the elements of the reticuloendothelium; 2) determining the percentage of dye absorbed from the blood colorimetrically; 3) determining the decrease, compared to normal, in the shift of pH in tissue culture (for example, spleen) and others.

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A. Bogomolets.