Neutrophils constitute the most numerous populations of peripheral blood leukocytes, fulfilling the fundamental role in the development of the innate immune response. As the cells of the first line of defense, they guard the organism against the spread of pathogenic microorganisms. Neutrophils, similar to the other cells of the immune system, enter the path of death after fulfilling their biological function. Depending on the conditions that they are found in, they may undergo different types of cell death which requires the involvement of numerous signaling pathways. In this review article, we summarize the current state of knowledge regarding the different forms of neutrophil death, such as apoptosis, necrosis, necroptosis, autophagy, NETosis and pyroptosis.

Neutrophils—polymorphonuclear cells (PMNs) are the cells of the initial immune response and make up the majority of leukocytes in the peripheral blood. After activation, these cells modify their functional status to meet the needs at the site of action or according to the agent causing injury. They receive signals from their surroundings and “plan” the course of the response in both temporal and spatial contexts. PMNs dispose of intracellular signaling pathways that allow them to perform a wide range of functions associated with the development of inflammatory processes. In addition to these cells, some protein complexes, known as inflammasomes, also have a special role in the development and maintenance of inflammation. These complexes participate in the proteolytic activation of key pro-inflammatory cytokines, such as IL-1β and IL-18. In recent years, there has been significant progress in the understanding of the structure and molecular mechanisms behind the activation of inflammasomes and their participation in the pathogenesis of numerous diseases. The available reports focus primarily on macrophages and dendritic cells. According to the literature, the activation of inflammasomes in neutrophils and the associated death type—pyroptosis—is regulated in a different manner than in other cells. The present work is a review of the latest reports concerning the course of inflammasome activation and inflammatory cytokine secretion in response to pathogens in neutrophils, as well as the role of these mechanisms in the pathogenesis of selected diseases.

To investigate the mechanism of apoptosis dependent on the Fas/FasL (Fas ligand) complex in the presence of N-nitrosodimethylamine (NDMA) in human leukocytes. Polymorphonuclear neutrophils (PMNs) and peripheral blood mononuclear cells (PBMCs) were isolated form whole blood by density centrifugation. The concentration of NDMA was assessed by cellular toxicity assay. Apoptotic cells were assessed with flow cytometry and the expression of pro- and antiapoptotic proteins was investigated by Western blotting in PMNs and PBMCs treated with NDMA and/or FasL. PMNs showed a higher ratio of apoptotic cells than PBMCs after exposure to NDMA and/or FasL. Enhanced apoptosis was related to the increased expression of proapoptotic proteins in neutrophils following exposure to either NDMA or FasL. In PBMCs, the relation was observed after exposure to FasL only. PMNs and PBMCs incubated with NDMA and FasL simultaneously demonstrated the highest increase in protein expression. NDMA shows a stronger proapoptotic effect with PMNs than with PBMCs. The Fas/FasL complex, along with other proapoptotic proteins of the receptor (Fas, FADD) and mitochondrial pathway (Noxa, Puma, Bim), plays a key role in the induction of neutrophil apoptosis. Synergic effects of NDMA and FasL which lead to higher induction of apoptosis in PMNs than in PBMCs indicates a multistage and varied regulation of apoptosis in different populations of leukocytes.

N-nitrosodimethylamine (NDMA) is a xenobiotic widespread in human environment capable of regulating the lifespan of immune cells. In this study, we examined the roles of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/death receptor 5 (DR5) complex and the Fas molecule in the induction of the extrinsic apoptosis pathway in human neutrophils (polymorphonuclear neutrophils (PMNs)) and peripheral blood mononuclear cells (PBMCs) exposed to NDMA. Also we assessed these proteins ability to trigger the intrinsic apoptosis pathway in those cells. For this purpose, we examined the expression of Fas-associated protein with death domain, truncated Bid (tBid) proteins, and apoptogenic factors such as apoptosis-inducing factor, Smac/Diablo, Omi/HtrA2, and caspase-3 as an indication of accomplished apoptosis phenomenon. PMNs and PBMCs were isolated from whole blood by density gradient centrifugation using Polymorphrep. Apoptotic cells were assessed with flow cytometry using a ready-made kit. The expression of proapoptotic molecules was investigated by Western blot analysis of PMNs and PBMCs treated with NDMA and/or rhTRAIL. The obtained results confirm the proapoptotic effects of NDMA on the examined human leukocytes and indicate an active participation of the TRAIL/DR5 complex and Fas protein in the process of apoptosis. Moreover, the research revealed distinct mechanisms of intrinsic apoptosis pathway activation between PMNs and PBMCs exposed to NDMA, as confirmed by the different levels of tBid, Smac/Diablo, Omi/HtrA2, and caspase-3 expression in those cells.

Neutrophils are the most numerous population of peripheral blood leukocytes and play a key role in innate immunity, participating in antibacterial, antifungal, antiviral, and antitumor responses. Their activity can be modulated by endogenous and exogenous factors, including pesticides, among which fungicides such as the commonly used imazalil (IMZ) constitute a significant group. The objective of this study was to assess the effect of IMZ (at an environmental dose of 0.07 ng/mL, as well as 10- and 100-fold higher doses) on selected functions of neutrophils. This study demonstrated that neutrophils incubated with IMZ at a dose detectable in the serum, exhibited lower phagocytotic capacity. In addition, at a 10-fold higher dose, this compound reduced the chemotactic capacity of neutrophils and led to increased activity of NADPH oxidase in these cells. Furthermore, it was observed that at the highest concentration used in this study IMZ intensified the production of nitric oxide. The exposure of neutrophils—the first line of defense—to IMZ affected their locomotion and pathogen-eliminating function. Moreover, the response of neutrophils was not proportionate to the concentration of IMZ used in the study.