The neutrophil as a cellular source of chemokines

Neutrophils are known to play an important role in inflammatory responses b y virtue of their ability to perform a series of effector functions that co llectively represent a major mechanism of innate immunity against injury an d infection. Zn recent years, however, it has become obvious that the contr ibution of neutrophils to host defence and natural immunity extends well be yond their traditional role as professional phagocytes. Indeed, neutrophils can be induced to express a number of genes whose products lie at the core of inflammatory and immune responses. These include not only Fc receptors, complement components, cationic antimicrobial and NADPH oxidase proteins, but also a variety of cytokines (including tumour necrosis factor-alpha, in terleukin (IL)-1 beta, IL-1R alpha, IL-12 and vascular endothelial growth f actor), and chemokines such as IL-8, growth-related gene product, macrophag e inflammatory protein (MLP)-1 alpha, MIP-1 beta, interferon-gamma -inducib le protein of 10 kDa and monokine induced by interferon-gamma. Because thes e chemokines are primarily chemotactic for neutrophils, monocytes, immature dendritic cells and T-lymphocyte subsets, a potential role for neutrophils in orchestrating the sequential recruitment of distinct leukocyte types to the inflamed tissue is likely to occur. The purpose of this review is to s ummarize the essential features of the production of chemokines by polymorp honuclear neutrophil leukocytes and the contribution that we have made to c haracterize some aspects of this newly discovered crucial function of neutr ophils.