Granule Protein Processing and Regulated Secretion in Neutrophils

Abstract

Neutrophils are part of a family of granulocytes that, together with eosinophils and basophils, play an essential role in innate immunity. Neutrophils are the most abundant circulating leukocytes and are vital for rapid immune responses, being recruited to sites of injury or infection within minutes, where they can act as specialized phagocytic cells. However, another prominent function of neutrophils is the release of pro-inflammatory compounds, including cytokines, chemokines, and digestive enzymes, which are stored in intracellular compartments and released through regulated exocytosis. Hence, an important feature that contributes to rapid immune responses is capacity of neutrophils to synthesize and store pre-formed pro-inflammatory mediators in specialized intracellular vesicles and thus no new synthesis is required. This review will focus on advancement in three topics relevant to neutrophil secretion. First, we will examine what is known about basal level pro-inflammatory mediator synthesis, trafficking, and storage in secretory compartments. Second, we will review recent advancements in the mechanisms that control vesicle mobilization and the release of pre-formed mediators. Third, we will examine the upregulation and de novo synthesis of pro-inflammatory mediators by neutrophils engaged at sites of infection.

The NET, the trap and the pathogen: neutrophil extracellular traps in cutaneous immunity

“…At inflammatory sites, neutrophils secrete de novo synthetized, as well as prestored cytokines to attract other immune cells [reviewed by Sheshachalam et al. and Amulic et al. ].…”

Targeting miR‐223 in neutrophils enhances the clearance of Staphylococcus aureus in infected wounds

“…In addition, the downregulation of miR‐223 promoted Il6 and Il1b transcription in a RAW264.7 macrophage cell line (Chen et al , ). Thus, miR‐223 might participate in trafficking pathways including the synthesis, storage, and secretion of bioactive substances and de novo synthesis of proinflammatory cytokines through transcriptional regulation (Sheshachalam et al , ).…”

Programming and memory dynamics of innate leukocytes during tissue homeostasis and inflammation

“…It is well known that neutrophils can perform diverse functions, such as phagocytosis, chemotaxis, toxin secretion via degranulation, and generation of NET [33]. With respect to degranulation, neutrophils have at least 3 distinct types of granules that have unique functions and can be differentially secreted in a context-dependent fashion [34]. Primary granules may be secreted when neutrophils encounter bacteria, virus, or fungi, whereas secondary granules are predominantly secreted for bactericidal purposes.…”