Biological Roles of Neutrophil-Derived Granule Proteins and Cytokines

Neutrophils, the most abundant white blood cells in human circulation, entertain intense interactions with other leukocyte subsets, platelets, and stromal cells. Molecularly, such interactions are typically communicated through proteins generated during granulopoiesis, stored in granules, or produced on demand. Here, we provide an overview of the mammalian regulation of granule protein production in the bone marrow and the de novo synthesis of cytokines by neutrophils recruited to tissues. In addition, we discuss some of the known biological roles of these protein messengers, and how neutrophil-borne granule proteins and cytokines can synergize to modulate inflammation and tumor development. Decoding the neutrophil interactome is important for therapeutically neutralizing individual proteins to putatively dampen inflammation, or for delivering modified neutrophil-borne proteins to boost host defense. Proteomics of neutrophils can provide an unbiased analysis of neutrophils, neutrophil subsets, and subcellular compartments.Granule proteins are produced during granulopoiesis and can provide a tool for rapid communication during the onset of inflammation.Neutrophils produce a large variety of cytokines with wide functional diversity, including stimulation and dampening of inflammation, angiogenesis, and wound healing.Neutrophil proteases cleave cytokines and chemokines, which can thereby alter their functional properties.Neutrophil granule proteins and cytokines might synergize in chronic inflammation and tumor development.