Mononuclear phagocyte system function in BALB/c mice: kinetic analysis of antibody-sensitized erythrocyte clearance in complement-depleted animals

Abstract

The mechanisms of immune clearance in normal BALB/c mice were studied by kinetic analysis of the clearance of immunoglobulin-sensitized red blood cells. A rate equation, derived from a model for the clearance of sensitized cells, was used to quantitate four rate constants regulating the individual rate-determining steps in the overall clearance process. A linear relationship was demonstrated between the level of antibody sensitization and constants regulating complement-dependent sequestration (k1), deactivation and release of cells back into the circulation (k2), complement-dependent phagocytosis (k4), and Fc-mediated sequestration and phagocytosis (k3). Clearance rate constants did not change with age in either female or male mice; nor was there a significant difference between the mean values in female versus male mice. The validity of the model was tested by altering serum complement levels to determine whether the predicted changes in complement-dependent rate constants k1, k2, and k4 would occur. Depletion of serum complement by cobra venom factor resulted in a significant decrease in complement-dependent sequestration (k1) and phagocytosis (k4) (p less than 0.001) but had no significant effect on Fc-mediated clearance function (k3). As serum complement was replenished, a greater-than-normal percentage of red blood cells sequestered by the complement clearance pathway underwent phagocytosis (k4) rather than being deactivated and released back into the circulation (k2). Demonstration that the derived rate constants are predictably sensitive to manipulation of a major clearance factor increases the confidence in using this technique and model to study immune clearance in experimental and naturally occurring disease states.