The Macrophages

Abstract

Macrophages were originally thought to play an important role in host defence against intracellular pathogenic micro-organisms. This observation led to the development of the concept of macrophage activation. The events required for macrophage activation have been extensively studied and clearly demonstrate that activation is brought about by soluble mediators secreted by stimulated T cells. Both natural and recombinant γ-IFN preparations have been shown to be capable of activating macrophages. The possibility that lymphokines other than γ-IFN, present in antigen- or mitogen-stimulated T-lymphocyte culture supernatants, participate in macrophage activation remains to be resolved. There seems to be little doubt that activated macrophages contribute to host defence mechanisms in the control of neoplasia. It has been shown that oxygen-dependent as well as independent mechanisms participate in the destruction of micro-organisms and neoplastic cells. Several soluble factors that kill bacteria and tumour cells in vitro and in vivo, released by activated macrophages, have been described. Of these, only TNF has been fully characterized by gene cloning studies and its amino acid sequence analysis. Similar studies need to be performed with guinea pig, mouse and human factors to confirm whether their activity is due to protein(s) coded by a single gene or family of genes.

Studies performed during the last 20 years have clearly established that macrophages, in addition to their function as effectors in host defence mechanisms, play a critical role in induction and regulation of immune response. Thus, it has been demonstrated that macrophages are required during the early events that lead to antigen-specific stimulation of T and B cells. These T cells, especially the helper subset, do not respond unless the antigen has undergone a processing and is associated with the products of the I-region of MHC. The macrophages, because of their innate capacity to take up and catabolize antigens and to express Ia, provide the necessary signals to helper T cells. This interaction between la-positive macrophages containing processed antigen and helper T cells results in secretion of lymphokine and DNA synthesis by T cells and synthesis of Ia molecules and lymphostimulatory molecules such as IL-1 by macrophages. However, the contribution of other la-positive cells in the induction of the immune response and the question of whether macrophages are the only cells that participate in immune induction requires further study.