The potential for monocyte-mediated immunotherapy during infection and malignancy. Part I: Apoptosis induction and cytotoxic mechanisms

The mononuclear phagocyte system consists of peripheral blood monocytes and tissue macrophages that collectively play a major role in host immunity. F ar from existing solely as phagocytic scavengers of cell debris and foreign matter. monocytes are highly active and responsive to inflammatory and imm unological signals that activate their microbicidal and tumoricidal functio ns. Cytokines that are secreted as an integral component of the innate immu ne response such as granulocyte-macrophage colony-stimulating factor (GM-CS F) and -IFN may directly activate the functions of the monocyte system. A k ey mediator of the effector functions of monocytes is tumour necrosis facto r (TNF) which transduces its signals upon binding to specific transmembrane receptors. TNF is highly cytotoxic to micro-organisms and susceptible mali gnant cells and in most cases delivers its cytotoxic signal to tumour cells by highly regulated mechanisms of programmed cell death or apoptosis. We b elieve that the numerous functions of the monocyte system may be harnessed for therapeutic gain both in the context of microbiological infection and m alignant disease. In this review, the mechanisms by which secreted and mono cyte cell-membrane-associated TNF induce apoptosis will be discussed. In ad dition, the cell-associated and secretory immunological mechanisms employed by monocytes in host defence will be discussed in the context of the their ability to combat infection and neoplasia.