The Mechanism of Blockade of the Reticuloendothelial System

Abstract

The rate of clearance of intravenously injected colloidal material is currently believed to be a measure of the phagocytic function of the reticuloendothelial system (RES). Furthermore, it has been assumed that the altered physiologic state observed following blockade of the RES is due to the inability of the RE cells to function as efficiently as before blockade (1, 2). The terms "blockade" and "saturation" of the RES imply that the phagocytic cells are either incapable of ingesting more material or that the rate at which additional particles can be ingested has been markedly retarded (3).The relationship between blockade of the RES and opsonin levels in blood has not been explored although recent evidence strongly suggests one (4). Plasma proteins and more specifically globulin fractions of plasma have been shown to be necessary for the phagocytosis of colloidal particles (5) and bacteria (6) in vitro. More recently the in vitro coating of particles by plasma proteins (7) and by a globulin fraction of plasma (8) enhanced their subsequent clearance in vivo. Although the nature of these plasma factors or opsonins for particulate material is in doubt it is generally assumed that they are nonspecific.In the present study the RES was blockaded with various colloidal materials and the effectiveness of the blockade was tested by the subsequent injection of a tracer dose of a similar or dissimilar colloid. It was felt that by using a tracer dose it might be more feasible to completely opsonize the relatively small number of particles, especially with a limited amount of opsonin, and thus provide a more specific test of the relationship of opsonin to blockade of the RES.In this report it will be demonstrated that blockade of the RES to tracer doses of colloidal material occurs only when the surface properties of the blockading and tracer colloids are similar. Gelatin when used as a colloidal stabilizing agent, confers specificity on the inert particle regardless of the type of particle used. It will be shown that homologous and heterologous plasma

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

“…Murray reported specificity of blockade on the blood clearance of various colloids (7). In our opinion, his failure to detect the slight blockading effect on dissimilar particles resulted from the fact that this effect is of short duration and of a magnitude difficult to detect without serial studies in the same animal.…”

“…As far as we have been able to determine, RES blockade has not been produced and characterized in man previously, although the phenomenon of blockade has been studied in experimental animals (7). The technique of the present study, a modification of that of Murray (7), afforded certain important advantages.…”

“…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.…”

Reticuloendothelial Function in the Isolated Perfused Liver IV. Phagocytosis of Aggregated-BSA and Colloidal Gold. Evidence for Nonspecific Opsonins

“…In prior studies, several investigations have brought forward evidence that blockade of the reticuloendothelial system can be attributed to depletion of opsonins (6)(7)(8). Others have argued that reticuloendothelial blockade is due to an alteration of the function of the RE cells (9)(10)(11).…”

The effect of RES blockade on red blood cell survival.

“…The present study is an attempt to evaluate the role of RES in red blood cell destruction, especially in the spleen. A modification of the technique employed by Murray (1963) was utilized in C3H mice. The RES was blockaded with heatdamaged red blood cells and the effectiveness of the blockade was tested by the subsequent injection of tracer dose of 59Fe-labeled red blood cells.…”