Histamine triggers the formation of neutrophil extracellular traps via NADPH oxidase, ERK and p38 pathways

Ershun Zhoua, Zhikai Wua, Xingyi Zhua, Peixuan Lia, Jingjing Wanga,b, Zhengtao Yanga,*

Abstract

Histamine plays a central role in various allergic diseases, such as allergic asthma and allergic rhinitis. Neutrophil extracellular traps (NETs) formation is a novel effector mechanism of neutrophils to defend against various stimuli. In this present study, we aimed to investigate the role of histamine on bovine NET formation, and examined its preliminary molecular mechanisms. Cell Counting Kit-8 (CCK8) and Lactate dehydrogenase assays showed that histamine had no significant influence on PMNs (polymorphonuclear leukocytes) viability. Confocal microscopy analyses identified NET structures by co-localizing the main components of NETs, and NET quantification revealed that histamine-triggered NETs were released in a dose-dependent manner. Furthermore, we found reactive oxygen species (ROS) production, phosphorylated extracellular signal-regulated kinase (ERK) and p38 proteins were significantly elevated in histamine-challenged PMNs. By applying functional inhibitors of nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase), ERK and p38, histamine-triggered NETs were markedly reduced, indicating their importance in histamine-triggered NET formation. Our findings described histamine-triggered NET formation, and revealed its potential molecular mechanisms via NADPH oxidase, ERK and p38 pathways. This is the first study to depict histamine-triggered NET formation, which could provide a new insight into histamine-related diseases.

Keywords:
Histamine
Neutrophils NETs
NADPH oxidase
Pathways

1. Introduction

Histamine is a natural constituent of the body classified as a biogenic amine (Best et al., 1927). Originally, it is only considered an inflammatory mediator causing anaphylactic reactions (Maintz and Novak, 2007). Nowadays, histamine is one of the most extensively studied biomolecules, and has been linked to various physiological functions, such as hematopoiesis, cell proliferation and differentiation, exocrine pancreatic secretion, embryonic development, regeneration, and wound healing (Akdis and Blaser, 2003; Haas and Panula, 2003; Jutel et al., 2002; Singh et al., 1997). Besides, histamine plays a vital role in the course of many allergic diseases such as allergic asthma and allergic rhinitis (Steelant et al., 2018; Yamauchi and Ogasawara, 2019). Laminitis from which cattle suffer is believed to be associated with histamine intolerance (histaminosis) (Mgasa, 1987). Subacute ruminal acidosis (SARA) often occur in high-producing lactating cows, which is due to the high concentrations of histamine produced in the rumen of dairy cows (Sun et al., 2017). Also, Histamine release induced by P. haemolytica leukotoxin seems an important factor in the pathogenesis of bovine pneumonic pasteurellosis (Adusu et al., 1994). PMNs are the most abundant leukocytes in blood that play a crucial role in innate immunity. Besides well-known phagocytosis and degranulation, the formation neutrophil extracellular traps (NETs) is a novel effector mechanism of neutrophils to defend against foreign invaders (Brinkmann et al., 2004; Fuchs et al., 2007), which has received extensive attention by researchers around the world since it was first reported in 2004. NETs are fine web-like structures composed of DNA as a backbone decorated with histones and numerous antimicrobial proteins released by neutrophils (Papayannopoulos, 2018), which can capture, neutralize and kill various microorganisms including bacteria, fungi (Urban et al., 2006), viruses (Saitoh et al., 2012) and parasites (Abi Abdallah et al., 2012). Moreover, some studies revealed that NETs hindered bacteria and fungi from disseminating (Branzk et al., 2014; Walker et al., 2007). However, one sword has two edges, if NETs are dysregulated, they can promote the pathogenesis of some immune-related diseases. Plenty of studies have showed that NETs also occur in noinfectious, sterile diseases, such as lupus nephritis (Bonanni et al., 2015), rheumatoid arthritis (Carmona-Rivera et al., 2020), diabetes (Berezin, 2019), atherosclerosis (Doring et al., 2017¨ ), vasculitis (Soderberg and Segelmark, 2018¨ ), thrombosis (Laridan et al., 2019), cancer (Erpenbeck and Schon, 2017¨ ), wound healing (Kaur et al., 2020) and trauma (Daniel et al., 2019). Regarding to NETs in cattle, increasing studies are emerging, among which NETs on bovine-related protozoan predominate (Grob et al., 2020; Mendez et al., 2018; Villagra-Blanco et al., 2017; Zhou et al., 2019). Recently, NETosis are also implicated in mycotoxins and trace elements-related diseases in cattle (Wang et al., 2020a, 2019; Zhou et al., 2020b). Therefore, NETs has been considered as potential therapeutic targets in many diseases.
Studies have showed that intranasal administration of recombinant DNase improved lung function in allergic diseases (da Cunha et al., 2016) indicating NETs’ importance. Considering that histamine is closely associated with allergic actions and symptoms, We speculated that histamine plays a crucial role in the formation of NETs. In this present study, we aimed to investigate whether histamine could induce the release of NETs by bovine PMNs, and further examined its preliminary mechanisms. 2. Materials and methods

2.1. Reagents

2,7-dichlorodihydrofluorescein diacetate (DCF-DA), Diphenyleneiodonium (DPI), 1,4-diamino-2,3-dicyano-1,4-bis [2-aminophenylthio] butadiene (U0126), SB202190, and zymosan are purchased from Sigma-Aldrich. Sytox Orange nucleic acid stain (Invitrogen), PicoGreen (Invitrogen), Histone H3 antibody (LSC353149; Life Span BioSciences, Inc), Myeloperoxidase (MPO) antibody (Orb16003; Biorbyt), anti-p38 (Bs3566; Bioworld), anti-ERK (Bs3627), anti-pp38 (Cell Signaling Technology Inc, USA), anti-p-ERK (Cell Signaling Technology Inc, USA) were used in this study.

2.2. Isolation of bovine PMNs

Three healthy 2-year old Chinese yellow cattle (female) were selected from a farm, and marked as blood donors. 20 mL peripheral blood was collected from each cattle each time, and PMNs (Polymorphonuclear leukocytes) were isolated using bovine PMNs isolation kit (TianJin HaoYang Biological Manufacture CO. China) according to the manufacturer’s instructions. Briefly, blood was diluted 1:1 with cleaning solution, layered on separating solution in centrifugal tubes, and then centrifuged at 700 g for 30 min. The lower cellular layer was collected, and washed by erythrocyte lysis solution until the cell pellet became white. Finally, isolated PMNs were re-suspended in RPMI 1640 medium without phenol red, and placed in a incubator until further use. The viability of neutrophils was measured by trypan blue dye, and the percentage of living cells was over 95 %. The purity of neutrophils can reach over 90 % according to our previous studies (Wang et al., 2020a, 2019). All animal experiments were performed in conformity with the Manual of Care and Use of Laboratory Animals published by the National Institutes of Health, and approved by the Institutional Animal Care and Use Ethics Committee at Jilin University (approval ID: SY201905017). In addition, it should be pointed out that all experiments can’t be finished once, therefore blood samples were collected many times from the three same cattle. For each experiment, we have three biological replicate, and two technical replicate.

2.3. Cytotoxicity assay by CCK-8 kit

This experiment was carried out using a CCK-8 kit (Cell Counting Kit- 8) (Cat NO. CA1210). Briefly, PMNs were seeded into a 96-well plate, stimulated by histamine (6.25, 12.5, 25 μM) for 2 h. Subsequently, 10 μL CCK-8 solution was added into each well. After 2 h incubation in an incubator, the plate was read by a plate reader at 450 nm.

2.4. Lactate dehydrogenase (LDH) assay

PMNs were seeded into a 96-well plate, and stimulated by histamine (6.25, 12.5, 25 μM) for 2 h. The plate was centrifuged at 400 g for 5 min, and the supernatants were transferred to a new plate. LDH activity was measured by LDH Cytotoxicity Assay kit (Beyotime Biotechnology, China) according to the manufacturer’s protocols.

2.5. Confocal microscopy analyses

PMNs were seeded on glass coverslips pre-treated with poly-L-lysine (0.1 mg/mL) and stimulated with histamine (25 μM) for 2 h at 37 ◦C with 5 % CO2. Then, samples were fixed with 4% (w/v) paraformaldehyde for 30 min. For immunostaining, paraformldehyde solution was removed, and samples were washed thrice with PBS (Phosphate buffered saline), followed by 1 h incubation with blocking buffer 3% BSA (bovine serum albumin). Labeling of specific proteins (histone and MPO) for NETs was performed with the incubation of anti-histone antibody or anti-myeloperoxidase antibody overnight, and secondary antibody goat-anti-rabbit conjugated to Alexa 488 for 2 h. For DNA staining, the samples were incubated with 5 μM Sytox Orange (dissolved in PBS) for 10 min in dark. Samples were observed and images were taken using confocal microscope (Olympus FluoView FV1000).

2.6. NETs quantification based on PicoGreen® fluorescent dye

In the first set of experiment, we quantified NETs induced by different concentrations of histamine (6.25, 12.5, 25 μM). PMNs were seeded in a 96-well plate, and then stimulated by histamine for 2 h in an incubator at 37 ◦C with 5 % CO2. Quant-iT™ PicoGreen solution was added into each well, and the fluorescence intensity was measured using an Infiniti M200 fluorescence plate reader (Tecan, Austria).
In the secondary set of experiment, we examined the effects of specific inhibitors on NET formation induced by histamine (25 μM) via NETs quantification. PMNs were pretreated with NADPH oxidase inhibitor (DPI, 50 μM), the inhibitors of ERK1/2-signaling pathway (U0126, 10 μM) and P38 MAPK-signaling pathway (SB202190, 10 μM) for 30 min in a 96-well plate, and then challenged by histamine for 2 h in an incubator with 37 ◦C and 5 % CO2. After adding PicoGreen solution, the plate was read by an Infiniti M200 fluorescence plate reader (Tecan, Austria) with 485 nm length of excitation and 535 nm length of emission. The concentration of all inhibitors were used based on our previous studies (Wang et al., 2020a, b).

2.7. ROS detection

PMNs were seeded into a 96-well plate, and stimulated by histamine (6.25, 12.5, 25 μM) for 2 h in an incubator with 37 ◦C and 5 % CO2. DCF- DA (10 μM) was added to each well, and the plate was incubated for 20 min. After thrice washing with PBS, fluorescence intensity was measured by an Infiniti M200 plate reader at 485 nm of excitation and 525 nm of emission.

2.8. Western blotting

For protein isolation, neutrophils were stimulated by histamine (6.25, 12.5, 25 μM) for 2 h, and then lysed with M-PER™ mammalian protein extraction reagent (Thermo Fisher Scientific). After centrifugation, the supernatant was collected, and protein concentration was measured by a bicinchoninic acid (BCA) protein assay reagent kit (Pierce).
For western blotting, first we separated proteins in samples using gel electrophoresis. The separated proteins were transferred onto polyvinylidene difluoride (PVDF) membrane. Next, the membrane was blocked with 3% BSA to prevent any nonspecific binding of antibodies, incubated with primary antibody (anti-p38 monoclonal antibody, 1:1000; anti-phosphor-p38 monoclonal antibody, 1:1000; anti-ERK monoclonal antibody, 1:1000; anti-phosphor-ERK monoclonal antibody, 1:1000) overnight at 4 ◦C, and incubated with HRP-conjugated secondary antibody for 2 h at room temperature. In the end, the membrane was detected using enhanced chemiluminescence (ECL) Plus Western Blotting Detection System (ProteinSimple, San Jose, CA, U.S. A.).

2.9. Statistical analysis

All Data were illustrated as means ± SEM of at least three biological replicates and two technical replicates. Graphs and statistical analyses were generated by using GrapPadPrism software (v.7.03). One-way analysis of variance (ANOVA) followed by Dunnett’s multiple comparison tests were used. Statistical significance was defined by a p value < 0.05.

3. Results

3.1. Histamine had no effect on PMN viability

First, we used CCK-8 assay to check the effect of histamine (6.25, 12.5, 25 μM) on PMN viability. The result showed that no obvious difference in cell viability was observed when neutrophils were stimulated by three different concentrations of histamine compared to the control group (Fig. 1A). Secondly, we checked the cellular cytotoxicity of histamine on PMNs via LDH assay. LDH is a cytosolic enzyme existing in many different types of cell, and extracellular LDH is an indicator of cellular cytotoxicity. Similarly, histamine (6.25, 12.5, 25 μM) challenge did not significantly change extracellular LDH level (Fig. 1B), indicating no cytotoxicity on PMNs.

3.2. Histamine triggered NET formation visualized by immunofluorescent staining

To visualize NET structures, PMNs were seeded onto coverslips and stimulated by 25 μM histamine for 2 h, and the samples were performed by immunostaining. NET structures were co-localized by DNA, histone and MPO staining. As shown in Fig. 2, NET formation induced by histamine was obviously observed (indicated by white arrows).

3.3. Histamine-triggered NET formation was dose-dependent

Here we chose three different concentrations of histamine (6.25, 12.5, 25 μM) to check if there is difference in NET formation. NETs quantification were conducted based on PicoGreen dsDNA reagent- derived fluorescent intensity. Compared to the control group, histamine induced an increasing extracellular DNA (1.99, 3.18, 5.60 times higher that control respectively) with increasing concentrations (Fig. 3), suggesting its dose-dependent manner in NET formation.

3.4. Histamine increased ROS production in a dose-dependent manner

ROS generation are required for NETs release(Kirchner et al., 2012). Here we measured intracellular ROS production in PMNs stimulated by histamine by DCF-DA. When compared to that of the control group, an increasing rising trend in ROS production induced by histamine (mean values of ROS production were 1.24, 1.41. 1.43 times higher than control group respectively) was observed (Fig. 4), indicating that histamine dose-dependently increased ROS generation.

3.5. Histamine enhanced the phosphorylation of ERK and p38 proteins

Mitogen-activated protein kinase (MAPK) pathways regulate a large range of cellular activities, such as gene expression, cell growth, metabolism, survival, apoptosis, and differentiation (Rezatabar et al., 2019). In this present study, phosphorylated ERK proteins were increased by 1.32, 1.64, 1.67 times respectively (Fig. 5), and phosphorylated p38 proteins were increased by 1.08, 1.41, 2.04 times respectively in histamine-treated PMNs, implying a potential role of ERK and p38-ralated MAPK pathways in NET formation.

3.6. Histamine-triggered NET formation was a NADPH oxidase, ERK and p38 pathways mediated process

To further examine the role of ROS, ERK and p38-mediated MAPK pathways in histamine-triggered NETs, we applied their functional inhibitors (SB202190, U0126, DPI respectively). In Fig. 6, histamine- induced extracellular DNA were significantly decreased to 56 % (SB202190), 45 % (U0126), 40 % (DPI) respectively with these inhibitors pretreatment. This finding showed that ROS, ERK and p38- mediated MAPK pathways played a crucial role in histamine-triggered NET formation.

4. Discussion

Histamine mainly stored in mast cells is a prominent mediator in the clinical symptoms of many allergic diseases, such as asthma, allergic rhinitis, urticaria, anaphylaxis. NETs as part of the innate immune response have been reported to be involved in diverse allergic and autoimmune diseases (Simon et al., 2013). Therefore, in this present study we described and characterized NET formation induced by histamine.
The process of NET formation is called NETosis, and it has been the most studied area of PMN functions since its first report. NETs are mainly composed of DNA, histones, and many granule proteins such as NE, MPO, cathepsin G, and lactoferrin. These classical components of NETs have been co-localized by immunostaining, and visualized under cofocal microscope to identify the structures of NETs (Rada, 2019; Zhou et al., 2019, 2020a). Here we identified histamine-triggered NET structures via co-localizing DNA, histone and MPO, and observed this kind of structures under cofocal microscope, suggesting histamine is a potent inducer of NETs.
Initially, most of studies focused on microorganisms-triggered NETs. As a vast number of molecules were identified as NETs stimuli such as ionomycin (Francis et al., 2014), nicotine (Hosseinzadeh et al., 2016), hydrogen peroxide (Fuchs et al., 2007), TNF-α (Keshari et al., 2012), Fc receptors (Urban et al., 2006), IFN-γ (Yousefi et al., 2008), and antimicrobial peptides (Neumann et al., 2014), increasing studies are paying attention on non-infectious and autoimmune diseases (Fousert et al., 2020; Kim et al., 2019). Histamine is a main mediator in allergic diseases, and we found it also can induce NET formation. Moreover, histamine-induced NETs were dose-dependent, which is similar to other stimuli (Lee et al., 2017; Mori et al., 2012). Two major types of NETosis have been found: NADPH oxidase (NOX)-dependent and NOX-independent NETosis (Rohm et al., 2014¨ ). NADPH oxidase is a crucial enzyme in host defense, and patients with deficiency of NADPH oxidase suffer from life-threatening infections (Segal et al., 2011). NADPH oxidase is the major source of ROS that play an important role in various biological processes (Filip-Ciubotaru et al., 2016). Histamine increased ROS production, and inhibition of NADPH oxidase significantly hindered NET formation induced by histamine, indicating that histamine-triggered NETosis is a NOX-dependent process. ERK and p38 MAPK pathways regulate a variety of cellular functions including NETosis (Keshari et al., 2013). It is known that ERK and p38 pathways are closely associated with NET formation via activation of NADPH oxidase (Hakkim et al., 2011), which is also confirmed in histamine-triggered NETosis by us. In this study, ERK and p38 proteins were increased in histamine-stimulated PMNs, and NETs induced by histamine were obviously decreased by functional inhibition of ERK and p38 pathways, showing the key role of this two pathways in histamine-triggered NETosis.
The versatile effects of histamine are mediated by four distinct G protein-coupled receptors, which has been identified as histamine receptors (HRs) and characterized. Studies on HRs have largely improved our understanding of the roles of histamine in diseases and treatment targeting HRs has been used for decades. Three different HRs are expressed in PMNs and play an important role in modulating the oxidative burst of PMNs (Benbarek et al., 1999; Cíˇz and Lojek, 2013). A study have revealed that histamine stimulated equine neutrophils to produce ROS and free readicals via H1 receptors and the NADPH-oxidase pathway (Benbarek et al., 1999). Given that NETosis is closely associated with ROS production and NADPH-oxidase pathway, hence, HRs could be crucial in histamine-induced NETosis.
In short, we illustrated histamine-triggered NET structures, and described its preliminary characters. The primary mechanism of histamine-triggered NETosis is dependent on NADPH oxidase, ERK and p38 pathways. However, further studies are still required to delineate the detailed mechanisms of histamine-triggered NETosis, especially the role of HRs in this process.

References

Abi Abdallah, D.S., Lin, C., Ball, C.J., King, M.R., Duhamel, G.E., Denkers, E.Y., 2012. Toxoplasma gondii triggers release of human and mouse neutrophil extracellular traps. Infect. Immun. 80, 768–777.
Adusu, T.E., Conlon, P.D., Shewen, P.E., Black, W.D., 1994. Pasteurella haemolytica leukotoxin induces histamine release from bovine pulmonary mast cells. Canadian journal of veterinary research = Revue canadienne de recherche veterinaire 58, 1–5.
Akdis, C.A., Blaser, K., 2003. Histamine in the immune regulation of allergic inflammation. J. Allergy Clin. Immunol. 112, 15–22.
Benbarek, H., Mouithys-Mickalad, A., Deby-Dupont, G., Deby, C., Grülke, S., Nemmar, A., Lamy, M., Serteyn, D., 1999. High concentrations of histamine stimulate equine polymorphonuclear neutrophils to produce reactive oxygen species. Inflamm. Res. 48, 594–601.
Berezin, A., 2019. Neutrophil extracellular traps: the core player in vascular complications of diabetes mellitus. Diab. Metab. Syndr. 13, 3017–3023.
Best, C.H., Dale, H.H., Dudley, H.W., Thorpe, W.V., 1927. The nature of the vaso-dilator constituents of certain tissue extracts. J. Physiol. 62, 397–417.
Bonanni, A., Vaglio, A., Bruschi, M., Sinico, R.A., Cavagna, L., Moroni, G., Franceschini, F., Allegri, L., Pratesi, F., Migliorini, P., Candiano, G., Pesce, G., Ravelli, A., Puppo, F., Martini, A., Tincani, A., Ghiggeri, G.M., 2015. Multi-antibody composition in lupus nephritis: isotype and antigen specificity make the difference. Autoimmunity reviews 14, 692–702.
Branzk, N., Lubojemska, A., Hardison, S.E., Wang, Q., Gutierrez, M.G., Brown, G.D., Papayannopoulos, V., 2014. Neutrophils sense microbe size and selectively release neutrophil extracellular traps in response to large pathogens. Nat. Immunol. 15, 1017–1025.
Brinkmann, V., Reichard, U., Goosmann, C., Fauler, B., Uhlemann, Y., Weiss, D.S., Weinrauch, Y., Zychlinsky, A., 2004. Neutrophil extracellular traps kill bacteria. Science 303, 1532–1535.
Carmona-Rivera, C., Carlucci, P.M., Goel, R.R., James, E., Brooks, S.R., Rims, C., Hoffmann, V., Fox, D.A., Buckner, J.H., Kaplan, M.J., 2020. Neutrophil extracellular traps mediate articular cartilage damage and enhance cartilage component immunogenicity in rheumatoid arthritis. JCI insight 5.
Cíˇz, M., Lojek, A., 2013. Modulation of neutrophil oxidative burst via histamine receptors. Br. J. Pharmacol. 170, 17–22. da Cunha, A.A., Nunez, N.K., de Souza, R.G., Moraes Vargas, M.H., Silveira, J.S.,˜
Antunes, G.L., Durante Lda, S., Porto, B.N., Marczak, E.S., Jones, M.H., Pitrez, P.M., 2016. Recombinant human deoxyribonuclease therapy improves airway resistance and reduces DNA extracellular traps in a murine acute asthma model. Exp. Lung Res. 42, 66–74.
Daniel, C., Leppkes, M., Munoz, L.E., 2019. Extracellular DNA traps in inflammation,˜ injury and healing. Nat Rev Nephrol. 15, 559–575.
Doring, Y., Soehnlein, O., Weber, C., 2017. Neutrophil extracellular traps in¨ atherosclerosis and atherothrombosis. Circ. Res. 120, 736–743.
Erpenbeck, L., Schon, M.P., 2017. Neutrophil extracellular traps: protagonists of cancer¨ progression? Oncogene 36, 2483–2490.
Filip-Ciubotaru, F., Manciuc, C., Stoleriu, G., Foia, L., 2016. NADPH OXIDASE: STRUCTURE AND ACTIVATION MECHANISMS (REVIEW). NOTE I. Revista medico- chirurgicala a Societatii de Medici si Naturalisti din Iasi 120, 29–33.
Fousert, E., Toes, R., Desai, J., 2020. Neutrophil extracellular traps (NETs) take the Central stage in driving autoimmune responses. Cells 9.
Francis, R.J., Butler, R.E., Stewart, G.R., 2014. Mycobacterium tuberculosis ESAT-6 is a leukocidin causing Ca2+ influx, necrosis and neutrophil extracellular trap formation. Cell Death Dis. 5, e1474.
Fuchs, T.A., Abed, U., Goosmann, C., Hurwitz, R., Schulze, I., Wahn, V., Weinrauch, Y., Brinkmann, V., Zychlinsky, A., 2007. Novel cell death program leads to neutrophil extracellular traps. J. Cell Biol. 176, 231–241.
Grob, D., Conejeros, I., Velasquez, Z.D., Pre´ ußer, C., Gartner, U., Alar¨ con, P., Burgos, R.´ A., Hermosilla, C., Taubert, A., 2020. Trypanosoma brucei brucei induces polymorphonuclear neutrophil activation and neutrophil extracellular traps release. Front. Immunol. 11, 559561.
Haas, H., Panula, P., 2003. The role of histamine and the tuberomamillary nucleus in the nervous system. Nature reviews. Neuroscience 4, 121–130.
Hakkim, A., Fuchs, T.A., Martinez, N.E., Hess, S., Prinz, H., Zychlinsky, A., Waldmann, H., 2011. Activation of the raf-MEK-ERK pathway is required for neutrophil extracellular trap formation. Nat. Chem. Biol. 7, 75–77.
Hosseinzadeh, A., Thompson, P.R., Segal, B.H., Urban, C.F., 2016. Nicotine induces neutrophil extracellular traps. J. Leukoc. Biol. 100, 1105–1112.
Jutel, M., Watanabe, T., Akdis, M., Blaser, K., Akdis, C.A., 2002. Immune regulation by histamine. Curr. Opin. Immunol. 14, 735–740.
Kaur, T., Dumoga, S., Koul, V., Singh, N., 2020. Modulating neutrophil extracellular traps for wound healing. Biomater. Sci. 8, 3212–3223.
Keshari, R.S., Jyoti, A., Dubey, M., Kothari, N., Kohli, M., Bogra, J., Barthwal, M.K., Dikshit, M., 2012. Cytokines induced neutrophil extracellular traps formation: implication for the inflammatory disease condition. PLoS One 7, e48111.
Keshari, R.S., Verma, A., Barthwal, M.K., Dikshit, M., 2013. Reactive oxygen species- induced activation of ERK and p38 MAPK mediates PMA-induced NETs release from human neutrophils. J. Cell. Biochem. 114, 532–540.
Kim, S.W., Lee, H., Lee, H.K., Kim, I.D., Lee, J.K., 2019. Neutrophil extracellular trap induced by HMGB1 exacerbates damages in the ischemic brain. Acta Neuropathol. Commun. 7, 94.
Kirchner, T., Moller, S., Klinger, M., Solbach, W., Laskay, T., Behnen, M., 2012. The¨ impact of various reactive oxygen species on the formation of neutrophil extracellular traps. Mediators Inflammation 2012, 849136.
Laridan, E., Martinod, K., De Meyer, S.F., 2019. Neutrophil extracellular traps in arterial and venous thrombosis. Seminars in Thrombosis and Hemostasis 45, 86–93.
Lee, J., Luria, A., Rhodes, C., Raghu, H., Lingampalli, N., Sharpe, O., Rada, B., Sohn, D. H., Robinson, W.H., Sokolove, J., 2017. Nicotine drives neutrophil extracellular traps formation and accelerates collagen-induced arthritis. Rheumatology (Oxford, England) 56, 644–653.
Maintz, L., Novak, N., 2007. Histamine and histamine intolerance. Am. J. Clin. Nutr. 85, 1185–1196.
Mendez, J., Sun, D., Tuo, W., Xiao, Z., 2018. Bovine neutrophils form extracellular traps in response to the gastrointestinal parasite Ostertagia ostertagi. Sci. Rep. 8, 17598.
Mgasa, M.N., 1987. Bovine pododermatitis aseptica diffusa (laminitis) aetiology, pathogenesis, treatment and control. Vet. Res. Commun. 11, 235–241.
Mori, Y., Yamaguchi, M., Terao, Y., Hamada, S., Ooshima, T., Kawabata, S., 2012. α-Enolase of Streptococcus pneumoniae induces formation of neutrophil extracellular traps. J. Biol. Chem. 287, 10472–10481.
Neumann, A., Vollger, L., Berends, E.T., Molhoek, E.M., Stapels, D.A., Midon, M.,¨ Friaes, A., Pingoud, A., Rooijakkers, S.H., Gallo, R.L., ˜ Morgelin, M., Nizet, V.,¨ Naim, H.Y., von Kockritz-Blickwede, M., 2014. Novel role of the antimicrobial¨ peptide LL-37 in the protection of neutrophil extracellular traps against degradation by bacterial nucleases. J. Innate Immun. 6, 860–868.
Papayannopoulos, V., 2018. Neutrophil extracellular traps in immunity and disease. Nature reviews. Immunology 18, 134–147.
Rada, B., 2019. Neutrophil extracellular traps. Methods in molecular biology (Clifton, N. J.) 1982, 517–528.
Rezatabar, S., Karimian, A., Rameshknia, V., Parsian, H., Majidinia, M., 2019. RAS/ MAPK Signaling Functions in Oxidative Stress, DNA Damage Response and Cancer Progression.
Rohm, M., Grimm, M.J., ¨ D’Auria, A.C., Almyroudis, N.G., Segal, B.H., Urban, C.F., 2014. NADPH oxidase promotes neutrophil extracellular trap formation in pulmonary aspergillosis. Infect. Immun. 82, 1766–1777.
Saitoh, T., Komano, J., Saitoh, Y., Misawa, T., Takahama, M., Kozaki, T., Uehata, T., Iwasaki, H., Omori, H., Yamaoka, S., Yamamoto, N., Akira, S., 2012. Neutrophil extracellular traps mediate a host defense response to human immunodeficiency virus-1. Cell Host Microbe 12, 109–116.
Segal, B.H., Veys, P., Malech, H., Cowan, M.J., 2011. Chronic granulomatous disease: lessons from a rare disorder. Biol. Blood Marrow Transplant. 17, S123–131.
Simon, D., Simon, H.U., Yousefi, S., 2013. Extracellular DNA traps in allergic, infectious, and autoimmune diseases. Allergy 68, 409–416.
Singh, J., Pariente, J.A., Salido, G.M., 1997. The physiological role of histamine in the exocrine pancreas. Inflamm. Res. 46, 159–165.
Soderberg, D., Segelmark, M., 2018. Neutrophil extracellular traps in vasculitis, friend or¨ foe? Curr. Opin. Rheumatol. 30, 16–23.
Steelant, B., Seys, S.F., Van Gerven, L., Van Woensel, M., Farr´e, R., Wawrzyniak, P., Kortekaas Krohn, I., Bullens, D.M., Talavera, K., Raap, U., Boon, L., Akdis, C.A., Boeckxstaens, G., Ceuppens, J.L., Hellings, P.W., 2018. Histamine and T helper cytokine-driven epithelial barrier dysfunction in allergic rhinitis. J. Allergy Clin. Immunol. 141, 951-963.e958.
Sun, X., Yuan, X., Chen, L., Wang, T., Wang, Z., Sun, G., Li, X., Li, X., Liu, G., 2017. Histamine induces bovine rumen epithelial cell inflammatory response via NF-κB pathway. Cell. Physiol. Biochem. 42, 1109–1119.
Urban, C.F., Reichard, U., Brinkmann, V., Zychlinsky, A., 2006. Neutrophil extracellular traps capture and kill candida albicans yeast and hyphal forms. Cell. Microbiol. 8, 668–676.
Villagra-Blanco, R., Silva, L.M.R., Munoz-Caro, T., Yang, Z., Li, J., ˜ Gartner, U.,¨ Taubert, A., Zhang, X., Hermosilla, C., 2017. Bovine polymorphonuclear neutrophils cast neutrophil extracellular traps against the abortive parasite neospora caninum. Front. Immunol. 8, 606.
Walker, M.J., Hollands, A., Sanderson-Smith, M.L., Cole, J.N., Kirk, J.K., Henningham, A., McArthur, J.D., Dinkla, K., Aziz, R.K., Kansal, R.G., Simpson, A.J., Buchanan, J.T., Chhatwal, G.S., Kotb, M., Nizet, V., 2007. DNase Sda1 provides selection pressure for a switch to invasive group a streptococcal infection. Nat. Med. 13, 981–985.
Wang, J.J., Wei, Z.K., Han, Z., Liu, Z.Y., Zhu, X.Y., Li, X.W., Wang, K., Yang, Z.T., 2019. Zearalenone induces estrogen-receptor-independent neutrophil extracellular trap release in vitro. J. Agric. Food. Chem. 67, 4588–4594.
Wang, J., Liu, Z., Han, Z., Wei, Z., Zhang, Y., Wang, K., Yang, Z., 2020a. Fumonisin B(1) triggers the formation of bovine neutrophil extracellular traps. Toxicol. Lett. 332, 140–145.
Wang, J.J., Wei, Z.K., Han, Z., Liu, Z.Y., Zhang, Y., Zhu, X.Y., Li, X.W., Wang, K., Yang, Z. T., 2020b. Sodium fluoride exposure triggered the formation of neutrophil extracellular traps. Environ. Pollut. (Barking, Essex : 1987) 257, 113583.
Yamauchi, K., Ogasawara, M., 2019. The role of histamine in the pathophysiology of asthma and the clinical efficacy of antihistamines in asthma therapy. Int. J. Mol. Sci. 20.
Yousefi, S., Gold, J.A., Andina, N., Lee, J.J., Kelly, A.M., Kozlowski, E., Schmid, I., Straumann, A., Reichenbach, J., Gleich, G.J., Simon, H.U., 2008. Catapult-like release of mitochondrial DNA by eosinophils contributes LY2228820 to antibacterial defense. Nat. Med. 14, 949–953.
Zhou, E., Conejeros, I., Velasquez, Z.D., M´ unoz-Caro, T., ˜ Gartner, U., Hermosilla, C.,¨ Taubert, A., 2019. Simultaneous and positively correlated NET formation and autophagy in besnoitia besnoiti tachyzoite-exposed bovine polymorphonuclear neutrophils. Front. Immunol. 10, 1131.
Zhou, E., Silva, L.M.R., Conejeros, I., Velasquez, Z.D., Hirz, M., ´ Gartner, U., Jacquiet, P.,¨ Taubert, A., Hermosilla, C., 2020a. Besnoitia besnoiti bradyzoite stages induce suicidal- and rapid vital-NETosis. Parasitology 147, 401–409.
Zhou, X., Wang, H., Lian, S., Wang, J., Wu, R., 2020b. Effect of Copper, Zinc, and Selenium on the Formation of Bovine Neutrophil Extracellular Traps.