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.
Highlights
Neutrophils are the most abundant leukocytes in blood, comprising 60–70% of all circulating white blood cells, and make up an essential part of both innate and adaptive immunity
The OP9 stromal cell line, which is derived from the osteopetrotic mouse, was selected since they lack production of macrophage-colony stimulating factor (M-CSF) and support neutrophil rather than macrophage differentiation [10, 11]
Protocols have been reported that differentiated neutrophils can be prepared from induced pluripotent stem cells [14,15,16]. These are significant advancements since the ability to obtain functional neutrophils from human embryonic stem cells (hESCs), iPSCs, and even patient-derived iPSCs may progress toward their eventual use in the treatment of hematopoietic disorders [17, 18]
Summary
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. 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. 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 no new synthesis is required. We will examine the upregulation and de novo synthesis of pro-inflammatory mediators by neutrophils engaged at sites of infection
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