Macrophage handling of soluble immune complexes

Twoin-vivo observations underline the importance of studying macrophage interactions with soluble immune complexes. The first is the clearance of soluble complexes from the circulation after experimental administration of free or complexed antigen, during an acute infection, or even after a heavy meal. Clearance is mediated by the mononuclear phagocyte system, particularly by the Kupffer cells of the liver, and its rate is dependent on both the macrophage-binding activity of the complexed antibodies and complex size. The second is the association of circulating immune complexes with diseases such as rheumatoid arthritis and systemic lupus erythematosus, where damage to specific organs and tissues is thought to be caused by complexes deposited at these sites. The basis of the persistence of soluble complexes in the blood, and the part played by the circulating, as opposed to the deposited, complexes in pathogenesis are aspects of these diseases in which the activity and responsiveness of mononuclear phagocytes may be extremely important. Studiesin vitro provide a valuable background for investigating the activitiesin vivo of soluble complexes by defining (i) the way in which macrophages recognize cytophilic antibodies and the basis of binding enhancement which follows antibody combination with antigen, (ii) the kinetics of complex uptake and destruction by phagocytes and the biochemical mechanisms involved; and (iii) the regulatory effect that soluble immune complexes may have on macrophage activities such as oxidative metabolism and lysosomal enzyme release. In this review, Graham Leslie outlines the progress that has been made in characterizing these events.