Studies of mononuclear phagocyte function in the rat. I. Saturation and recovery following intravenous administration of soluble human serum albumin (HSA)--anti-HSA complexes.

We have attempted to demonstrate saturation of the mononuclear phagocyte system (MPS) in the Long Evans rat following intravenous administration of increasing doses of soluble HSA--125I-anti-HSA complexes. The fate of large (greater than 11S) complexes was followed by sucrose density gradient ultracentrifugation of serial serum samples in rats receiving 0.005-0.16 mg anti-HSA/g body weight. Administration of complexes provoked a rapid and profound increase in vascular permeability. Under these conditions no steady state clearance velocity for greater than 11S complexes could be established. The quantity of greater than 11S complexes removed from the circulation in the 1st hr never became independent of the initial dose. Specific immune complex uptake by the liver reached a maximum in rats receiving 0.09 mg anti-HSA/g body weight. Above this dose specific uptake decreased. Clearance of a tracer dose of complexes in rats pre-loaded with complexes containing 0.06 mg anti-HSA/g body weight was delayed for more than 3 hr. This was cautiously interpreted to indicate the period required for MPS recovery. The pattern of immune complex clearance in the context of marked changes in vascular permeability raised the possibility that maximum uptake was determined not by saturation of the mononuclear phagocyte system but by impaired hepatic perfusion.