APOPTOSIS OR PROGRAMMED CELL DEATH is a physiological form of cell suicide that is profoundly influenced by the extracellular microenvironment. Apoptosis is characterized by a cascade of genetic and biochemical events that cause cell shrinkage, condensation of cytoplasmic and nuclear material, cleavage of chromosomal DNA into oligonucleosomesized (approximately 200 bp) fragments, and enhanced recognition of the dying cell by phagocytes. Apoptosis differs fundamentally from necrosis, the pathological form of cell death, in which the cell swells and lyses. The capacity to selectively induce apoptosis in leukocytes might be an important physiological mechanism for controlling accumulation of these cells in inflammatory lesions. In this paper, we review our data on apoptosis in human monocytes, cells which contribute both to the persistence and resolution of chronic inflammation. Apoptosis can be initiated when monocytes are cultured in the absence of appropriate exogenous stimulation. For example, addition of chemotactic factors is insufficient to block apoptosis. However, apoptosis in monocytes can be inhibited by adherence in the presence of serum, by microbial products such as lipopolysaccharide, or by certain pro-inflammatory cytokines, such as interleukin 1 and tumor necrosis factor-alpha. Cytokines derived from type 1 helper T cells (e.g., interferon-gamma) inhibit apoptosis whereas those derived from type 2 helper T cells (e.g., interleukin-4) enhance apoptosis in activated monocytes. Thus, cytokines derived from monocytes as well as T cells modulate apoptosis, implicating both autocrine and paracrine regulatory circuits in monocyte survival. The capacity to therapeutically regulate monocyte apoptosis promises to have tremendous value in promoting rapid healing or reducing the immunopathogenesis of chronic inflammation.
