This Research Topic is part of a series:
Pharmacological Approaches Targeting Neutrophilic InflammationNeutrophils (or polymorphonuclear leukocytes, PMNL) are the most abundant white blood cells with vital functions in the innate immune system. In the innate immune system, neutrophils are the first line of defense against infections and tissue injury. During the inflammatory response, neutrophils are recruited to inflammatory loci initiating the generation and release of PMNs-derived oxidants and proteases, playing a major role in the inflammatory response as well as in its resolution. Properly regulated innate immune response is essential both for the elimination of invading pathogens and for subsequent restoration of tissue homeostasis.
Neutrophilic inflammation occurs in response to infection, but the recruitment of neutrophils and activation of their microbicidal activity eventually work as adjuvant for adaptive immunity. Neutrophils not only clear pathogens, they also communicate with other cells. Neutrophil-derived molecules control the inflammatory response of dendritic cells, monocytes and macrophages, and depletion of neutrophils may have dramatic consequences, as neutrophils play a major role in dampening inflammation as well. Neutrophils play a major role in cancer-related inflammation too. The presence of anti-neutrophil and anti-myeloperoxidase antibodies (ANCAs) in many cancer environments emphasizes their importance for tumor immunology. Neutrophils interact with cancer cells and immune cells in order to shape the overall immune response.
The actual contribution of PMNLs in driving and resolution of inflammation needs to be clarified. Current research is focused on understanding the fundamental mechanisms that control the activation and regulation of innate immune function of neutrophils. These include pathogen recognition by pathogen-associated molecular patterns (PAMP), signaling to ROS and NO production, degranulation, chemotaxis, phagocytosis, and for controlling apoptosis and NETosis.
Pharmacological approaches aim to suppress or to potentiate immune responses according to the body needs. Pharmacological interference at all stages of neutrophil activation may be helpful in fighting against various inflammatory diseases. Intervention in the excessive production of oxidizing agents and NO, as well as in NETs production related to ANCAs are also of great interest. The capacity of neutrophils to regulate inflammatory and immune responses is dependent on the release of neutrophil-derived molecules. Eicosanoids are important mediators of neutrophilic inflammation, and pharmacological interference with their synthesis is of special interest. Approaches focusing on neutrophil-bacteria interaction and modulation of neutrophil responses by oligodeoxynucleotides, peptides and other compounds are also relevant.
We would like to urge researchers to describe new phenomena in neutrophil biology.
In this Research Topic we aim to highlight recent advances in the understanding of cellular mechanisms controlling neutrophil activation and new approaches to manipulate their immune regulatory properties. This paper collection will highlight the important role that neutrophil defense mechanisms play in driving and resolution of inflammation. We welcome the submission of Original Research, Reviews, Mini Reviews and Opinion articles focusing on, but not limited to, the following subtopics:
1. Targets and signaling pathways aimed at modulating neutrophilic functions in inflammation
2. Pathways to neutrophils over-activation, NETs release and neutrophilic inflammation. Role of cytonemes and NETs in signaling events in immune cells
3. New targets for the development of anti-inflammatory drugs