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

Intravascular clearance rates of gelatin-stabilized gold were compared with circulating titers of gelatin agglutinins in rats at increasing time intervals after blockading injections of gelatin-stabilized gold and S. marcescens endotoxin. The degree and duration of reticuloendothelial system (RES) blockade against the homologous colloid were directly related to the circulating levels of gelatin agglutinins. In contrast, plasma agglutinins were not decreased in endotoxin-induced blockade against the gelatin-stabilized colloid. In a further experiment, the plasma response to blockading injections of colloidal thorium dioxide, iron oxide, and zymosan was characterized by a transient increase in gelatin agglutinins suggesting the nonspecific release of opsonins from an extravascular source. The findings indicated that clearance rates of gelatin-stabilized colloids were dependent on the total available opsonin in the rat rather than the total circulating opsonin. It is suggested that RES blockade is effected by the prior nonspecific depletion of opsonins from an extravascular reserve which is the major component of the total available opsonin.

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