Studies on the physiology of macrophage receptors for alpha-macroglobulin X protease complexes.

Alveolar macrophages exhibit high-affinity receptors that effect the binding and internalization of alpha-macroglobulin X protease complexes (alpha M X P). Studies were designed to probe the mechanism of internalization of alpha M X P complexes. Macrophages also exhibit receptors capable of clearing other injurious agents such as mannose-terminal glycoproteins. We have demonstrated that uptake of mannose-terminal glycoproteins does not affect the rate of internalization of alpha M X P complexes, suggesting that "scavenger" receptors function independently, and that the machinery for endocytosis is not rate limiting. We have also demonstrated that the rate of internalization of receptor-bound alpha M X P is independent of receptor occupancy. During the internalization of alpha M X P there is a decrease in the number of surface receptors consistent with the internalization of ligand-receptor complexes. Using photoaffinity-labeled alpha M X P to inactivate surface receptors, we have demonstrated that even in the absence of ligand accumulation, pools of intracellular receptors exist which are capable of being exteriorized to the cell surface. These results suggest that concomitant with internalization of occupied receptors is the appearance of unoccupied receptors on the cell surface from an internal pool.