Complex aggregation: a critical event in macrophage handling of soluble immune complexes

IgG-containing soluble immune complexes are bound by macrophages and trigger activities, such as lysosomal enzyme release and the synthesis of reactive oxygen metabolites, which are involved in the phagocyte's attack on target organisms(1). Complexes are ingested at a rate four fold faster than the rate of membrane internalization associated with fluid phase pinocytosis(2,3) (a constitutive activity of macrophages) and the rate of ingestion is independent of complex size(2). One explanation offered for these observations is that complex endocytosis is preceded by rapid reorganization of the small membrane-bound complexes into large aggregates which may either initiate the ingestion process or congregate selectivity at the sites of forming pinosomes(2). Complex aggregation was viewed as occurring by a mechanism analogous to that of the patch formation induced by cross-linking native-bound IgG, on macrophages, with F(ab(1))2 fragments of anti-Ig antibodies(4). Here Graham Leslie discusses recent studies of complex re-arrangement at the macrophage surface that have provided a detailed theoretical framework to account for the phenomenon and have established the critical importance of this event in the efficient ingestion of membrane-bound complexes and soluble complex clearance from the circulation.