Receptor Mediated Uptake Of Fibrin Monomer
Electron microscopy of macrophages exposed to fibrinogen solutions containing dissolved fibrin that was labelled with heme-octapeptide for cytochemical detection indicated that 1) the fibrin became adsorbed in a monomeric rather than aggregated form at saturating levels on the cell surface over a 2-5 min. period, 2) the adsorbed fibrin was fully internalized by vesicular uptake and fused with lysosomal bodies over a subsequent 30-60 min, and 3) a loss of adsorptive capacity of the cell surface for uptake of more fibrin accompanied internalization of fibrin. The uptake of fibrin in monomeric form despite its existence in aggregated but dissociable form in solution indicated that the fibrin was being adsorbed by a receptor with affinity for the same sites that participate in aggregation, sites that are exposed by release of fibrinopeptide A. Removal of fibrinopeptide B itself does not induce high affinity uptake. By analogy to the loss of adsorptive capacity accompanying internalization of the fibrin by macrophages, clearance of monomer from the circulation also appears to depend on a consumable receptor in that initial rates of clearance of 125I-labelled monomer at high dosages (>1 mg/kg) follow kinetics of a 2nd order chemical reaction, while pseudo-first order kinetics apply with low dosages (<0.3 mg/kg). A requirement of dissociability of monomer from soluble complexes for rapid uptake is indicated by observation that the poorly dissociable form of fibrin lacking both fibrinopeptides A and B is cleared from the circulation at a very slow rate compared to fibrin lacking A alone. Importance of dissociability is indicated also by observation that injection of Factor XIIIa inhibits uptake to a degree comparable to removal of both A and B. The demonstration of monomer uptake indicates that clearance of fibrin may precede its deposition in aggregated form. It is suggested that the rapid but saturable uptake of monomer may proceed independently of phagocytosis of macroaggregates.