Die Sekretion von Mediatoren der Entzündung und der antimikrobiellen Abwehr durch Makrophagen

Abstract

Macrophages are highly differentiated mononuclear phagocytes which originate from stem cells of the bone marrow. The secretory potential of these cells has been recognized in recent years. Major secretory products comprise lysosomal enzymes, complement proteins, prostaglandins and interferon. Secretion of lysosomal hydrolases and proteinases is most prominent in macrophages stimulated in vivo or in vitro (Fig. 4). Lysosomal enzyme secretion may be an important factor in the induction and maintenance of inflammatory reactions. Complement (C) proteins secreted by macrophages belong to the classical activation unit (C1, C4 and C2), alternative activation unit (C3, B, D, P) and to the group of delayed-acting C proteins (Fig. 7). Therefore macrophages produce at local sites the C component C3 from which biologically active C3 fragments (C3a, C3b, C3e) can be generated. These C3 fragments mediate inflammatory and cytotoxic reactions and also promote phagocytic processes (Fig. 6). Cleavage of secreted C3 into the active fragments may occur by enzymes derived from both C activation units or by secreted lysosomal proteinases (Fig. 8). Stimulated macrophages also synthesize and release prostaglandins. These compounds which have inflammatory as well as antiinflammatory effects (Fig. 12) may play an important regulatory role in inflammatory processes. Interferon has been also recognized as a secretory product of macrophages. This substance supports antimicrobial resistance by its phagocytosis-increasing effect and its antiviral activity. The secretory function of macrophages as well as the biological effects of secreted mediators are highly susceptible to modulation. Thus, C3 fragments stimulate the secretion of lysosomal enzymes (Fig. 6) whereas prostaglandins inhibit their release (Fig. 12). The inflammatory reactions induced by lysosomal enzymes may be further increased by the generation of C3b which stimulates additional lysosomal enzyme release (Fig. 4). These and other examples suggest that endogenous control mechanisms may have a strong influence on the secretory function of macrophages as well as on the biological activity of secreted mediators.