Molecular biology of neutrophil differentiation.

Myeloid precursors undergo striking morphologic and functional changes during the process of granulocytic maturation. These changes are associated with significant changes in cell size and nuclear shape, and with the development of stage-specific organelles which contain proteins necessary for the highly specialized roles of neutrophils in phagocytosis, in bacterial killing, and in mediating the inflammatory response. This complex process reflects a carefully regulated and sequential pattern of gene expression, which only recently has begun to be understood at the molecular level. The critical signals for the neutrophil differentiation program are postulated to derive from cytokines, and these cytokines are thought to induce a series of maturational events primarily by transcriptional regulation of sequentially expressed genes. Recent studies have identified a large number of transcriptional regulators, both positive and negative, that appear to act in concert in the developing neutrophil. These genes drive the complex and delicately timed sequence of genetic events that takes the cell from a progenitor to a functionally active neutrophil. Many of these genes are expressed throughout neutrophil differentiation, however, and the ongoing challenge is to elucidate how the function of these factors is modulated to allow the induction of sequential gene expression.