Clearance rate in relation to agglutinins for gelatin-stabilized colloid in the rat

Abstract

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.

The Dynamics of Reticuloendothelial Blockade

“…The majority of such investigations have concluded that reticuloendothellal system (RES) blockade is the result of saturation of the phagocytic capacity of the system (2)(3)(4), or saturation of clones of phagocytic cells which remove the specific particles under study (5). However, recent observations have suggested that RES blockade may be caused by depletion of specific serum opsonins by the preliminary blockading injection (6)(7)(8). The current experiments were undertaken to resolve these conflicting views.…”

Function of the Reticuloendothelial System

“…Moreover, this same author has reported that the degree and duration of reticuloeudothelial blockade to gelatin-stabilized colloidal gold induced by the same colloid was directly related to the circulating level of gelatin agglutinins and he suggested that opsonins rather than saturation of the phagocytic cell provided the limiting factor in the clearance rates. This is particularly interesting in relation to the present study on serum factors and carbon clearance when it is appreciated that the rate of clearance of colloidal carbon is itself decreased as the content of gelatin increases and that with increasing gelatin in the carbon preparation there is an exponential prolongation in the duration of inhibition to a given albumin dose (15). Whether the factor that adsorbs onto barium sulfate is indeed a gelatin agglutinln or is some other component of serum is not apparent from the present study and must await further clarification.…”

“…The participation of a serum factor in intravascular clearance has been suggested by several authors. Thus clearance rates have been related to changes in gamma-globulin (22) and in serum titers of complement (5) and antibody (15,23). Although studies relating clearance to antibody or complement usually refer to bacterial clearances, there is some evidence that serum proteins may also participate in the clearance of inert colloids as well.…”

“…In the experiments reported here advantage was taken of the observation that denatured albumin injected while carbon is circulating depresses the rate of colloidal carbon clearance in a regular and predictable way. In a previous publication we reported that quantitative relationships exist between the dose of albumin and the onset and duration of carbon clearance inhibition (15 duration of inhibition to a given albumin dose. Since one effect of gelatin is to render the particle more stable in the blood it seemed reasonable to explore the possibility that the relationships found between albumin and carbon might represent a competition between the particles for an available serum factor.…”

“…The study of phagocytosis in ~/vo has depended on measuring the rate of dearance from the blood of foreign or altered autologous particulate substances, and an alteration in the rate of clearance has been observed following prior injection of identical or similar material (11). This reduction in the rate of clearance has been termed "reticuloendothelial blockade" and it has been suggested that it results either from saturation of the phagocytic cell (12) or from depletion of available serum opsonins (13)(14)(15). Jenkin and Rowley reported that treating carbon with serum prior to injection enhanced the clearance and, furthermore, prevented the "blockading effect" of prior carbon administration (13).…”