• Asian-Australasian Journal of Animal Sciences
• /
• v.26 no.10
• /
• pp.1406-1415
• /
• 2013

The study was conducted to correlate the periparturient immune status in terms of neutrophil functions and cytokine expression in peripheral blood mononuclear cell culture with impending postpartum reproductive disorders in buffaloes. Forty pregnant buffaloes were observed for occurrence of postpartum reproductive disorders (PRD), i.e., metritis, endometritis and delayed uterine involution etc., during one week prepartum to four weeks postpartum period. A representative number (n = 6) of buffaloes that did not develop any PRD were included in group I (healthy, control), while the animals which experienced PRD were assigned into group II (PRD, n = 8). The blood samples were collected at weekly interval from one week prepartum to four weeks postpartum period considering the day of calving as 'd 0'. Differential leucocytes counts, superoxide and hydrogen peroxide production activity in isolated neutrophils and the mRNA expression profile of cytokines i.e., IL-2, IL-4 and IFN-${\gamma}$ in PBMC culture were studied in all the samples. A higher total leucocytes, neutrophil and band cells count along with impaired neutrophil functions i.e., lowered level of production of superoxide and hydrogen peroxide before parturition and during early postpartum period were observed in buffaloes developing PRD. Further, a lower expression of IL-2, IFN-${\gamma}$ and IL-4 mRNA in PBMC culture was observed at calving in buffaloes that subsequently developed PRD at later postpartum. Thus, suppression in neutrophil function and cytokine expression at prepartum to early postpartum period predisposes the buffaloes to develop postpartum reproductive disorders. Hence, monitoring of neutrophils function and cytokine expression profile would be effective to predict certain reproductive disorders at late pregnancy or immediately after parturition in buffaloes. In future, this may be a novel approach for determining suitable management and therapeutic decisions for prevention of commonly occurring reproductive disorders in farm animals.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.16 no.5
• /
• pp.1048-1054
• /
• 2002

Silsosangami(SSG) is a formula of oriental medicines as an effective biological response modifier for augmenting host homeostasis of body circulation. Also SSG has been known to have an anti-diabetic activity and anti-platelet aggregation activity. The present study was undertaken to examine the effects of a new SSG on murine macrophage and human neutrophil functions as well as on several enzymes relevant to the inflammatory process. The results of the present study indicate that SSG exerts anti-inflammatory effects related to the inhibition of neutrophil functions and of PGE2 production, which could be due to a decreased expression of and COX-2.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.20 no.5
• /
• pp.1295-1302
• /
• 2006

Our preliminary aim is to elucidate the pharmacokinetic features of the PNS(Panax notoginseng Buck F.H. Chen. (Arialiaceae) root). First, we assessed the prevention of neurtrophil functions. A Panax notoginseng inhibited neutrophil functions, including degranulation, superoxide generation, and leukotriene B4 production, without any effect on 5-lipoxygenase activity. This Panax notoginseng reduced nitric oxide (NO) and prostaglandin E2 production in mouse peritoneal macrophages stimulated with lipopolysaccharide, whereas no influence on the activity of inducible NO synthase, cyclo-oxygenase-2 or cyclo-oxygenase-1 was observed. Panax notoginseng significantly reduced mouse paw oedema induced by carrageenan. The results indicate that Panax notoginseng exerts anti-inflammatory effects related to the inhibition of neutrophil functions and of NO and prostaglandin E2 production, which could be due to a decreased expression of inducible NO synthase and cyclo-oxygenase-2.

• The Korean Journal of Physiology and Pharmacology
• /
• v.26 no.4
• /
• pp.229-238
• /
• 2022

Severe bacterial infections are frequently accompanied by depressed neutrophil functions. Thus, agents that increase the microbicidal activity of neutrophils could add to a direct antimicrobial therapy. Lysophosphatidylcholine augments neutrophil bactericidal activity via the glycine (Gly)/glycine receptor (GlyR) α2/TRPM2/p38 mitogen-activated protein kinase (MAPK) pathway. However, the direct effect of glycine on neutrophil bactericidal activity was not reported. In this study, the effect of glycine on neutrophil bactericidal activity was examined. Glycine augmented bactericidal activity of human neutrophils (EC₅₀ = 238 μM) in a strychnine (a GlyR antagonist)-sensitive manner. Glycine augmented bacterial clearance in mice, which was also blocked by strychnine (0.4 mg/kg, s.c.). Glycine enhanced NADPH oxidase-mediated reactive oxygen species (ROS) production and TRPM2-mediated [Ca²⁺]_i increase in neutrophils that had taken up E. coli. Glycine augmented Lucifer yellow uptake (fluid-phase pinocytosis) and azurophil granule-phagosome fusion in neutrophils that had taken up E. coli in an SB203580 (a p38 MAPK inhibitor)-sensitive manner. These findings indicate that glycine augments neutrophil microbicidal activity by enhancing azurophil granule-phagosome fusion via the GlyRα2/ROS/calcium/p38 MAPK pathway. We suggest that glycine could be a useful agent for increasing neutrophil bacterial clearance.

• The Korean Journal of Physiology and Pharmacology
• /
• v.24 no.1
• /
• pp.1-10
• /
• 2020

Autophagy is a highly conserved intracellular degradation and energy-recycling mechanism that contributes to the maintenance of cellular homeostasis. Extensive researches over the past decades have defined the role of autophagy innate immune cells. In this review, we describe the current state of knowledge regarding the role of autophagy in neutrophil biology and a picture of molecular mechanism underlying autophagy in neutrophils. Neutrophils are professional phagocytes that comprise the first line of defense against pathogen. Autophagy machineries are highly conserved in neutrophils. Autophagy is not only involved in generalized function of neutrophils such as differentiation in bone marrow but also plays crucial role effector functions of neutrophils such as granule formation, degranulation, neutrophil extracellular traps release, cytokine production, bactericidal activity and controlling inflammation. This review outlines the current understanding of autophagy in neutrophils and provides insight towards identification of novel therapeutics targeting autophagy in neutrophils.

• Biomedical Science Letters
• /
• v.26 no.3
• /
• pp.226-229
• /
• 2020

S100A8 functions as an essential factor in inflammatory response. Cytokine release of monocytes and regulation of neutrophil apoptosis are important steps in pathogenesis of allergy. This study aims to examine the relation between cytokine release of monocytes due to S100A8 and neutrophil apoptosis. S100A8 enhanced the release of IL-6 and IL-8 in monocytes of normal and allergic subjects. Treatment of supernatants of normal and allergic monocytes with S100A8 blocked neutrophil apoptosis by inhibition of caspase 9 and caspase 3 activation. The secretion signal induced by S100A8 is involved in TLR4, Src family protein, PKCδ, ERK1/2, p38 MAPK, JNK, and NF-κB. These findings may contribute to understanding the complex pathogenesis of allergic diseases by determining inflammatory responses associated with S100A8, monocytes, and neutrophils.

• BMB Reports
• /
• v.55 no.10
• /
• pp.473-480
• /
• 2022

Neutrophils, the most abundant innate immune cells, play essential roles in the innate immune system. As key innate immune cells, neutrophils detect intrusion of pathogens and initiate immune cascades with their functions; swarming (arresting), cytokine production, degranulation, phagocytosis, and projection of neutrophil extracellular trap. Because of their short lifespan and consumption during immune response, neutrophils need to be generated consistently, and generation of newborn neutrophils (granulopoiesis) should fulfill the environmental/systemic demands for training in cases of infection. Accumulating evidence suggests that neutrophils also play important roles in the regulation of adaptive immunity. Neutrophil-mediated immune responses end with apoptosis of the cells, and proper phagocytosis of the apoptotic body (efferocytosis) is crucial for initial and post resolution by producing tolerogenic innate/adaptive immune cells. However, inflammatory cues can impair these cascades, resulting in systemic immune activation; necrotic/pyroptotic neutrophil bodies can aggravate the excessive inflammation, increasing inflammatory macrophage and dendritic cell activation and subsequent T_H1/T_H17 responses contributing to the regulation of the pathogenesis of autoimmune disease. In this review, we briefly introduce recent studies of neutrophil function as players of immune response.

• IMMUNE NETWORK
• /
• v.21 no.2
• /
• pp.16.1-16.8
• /
• 2021

Patients with severe coronavirus disease 2019 (COVID-19) demonstrate dysregulated immune responses including exacerbated neutrophil functions. Massive neutrophil infiltrations accompanying neutrophil extracellular trap (NET) formations are also observed in patients with severe COVID-19. However, the mechanism underlying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced NET formation has not yet been elucidated. Here we show that 2 viral proteins encoded by SARS-CoV-2, the nucleocapsid protein and the whole spike protein, induce NET formation from neutrophils. NET formation was ROSindependent and was completely inhibited by the spleen tyrosine kinase inhibition. The inhibition of p38 MAPK, protein kinase C, and JNK signaling pathways also inhibited viral protein-induced NET formation. Our findings demonstrate one method by which SARSCoV-2 evades innate immunity and provide a potential target for therapeutics to treat patients with severe COVID-19.

• BMB Reports
• /
• v.36 no.6
• /
• pp.565-571
• /
• 2003

The locomotor responses of human peripheral blood neutrophils and lymphocytes were measured by the change from spherical to polarized shapes in the presence of endotoxins (lipopolysaccharide, LPS) of enteric pathogens: S. dysenteriae type 1, V. cholerae Inaba 569B, S. typhimurium, and K. pneumoniae. We reported earlier that these endotoxins are chemotactic factors for the neutrophils since they stimulated cell polarization within a few minutes of incubation. Endotoxins had an inhibitory effect upon neutrophil phagocytosis of opsonized yeast and the cells engulfed fewer yeasts. Interestingly, endotoxins increased neutrophil adhesion to clean glass surfaces, but stimulated the cells to exhibit increased random locomotion (chemokinesis) through cellulose nitrate filters and show an enhanced ability to reduce nitroblue tetrazolium (NBT) dye. Unlike neutrophils, lymphocytes direct from blood do not show polarized morphology towards chemotactic factors but the cells acquire locomotor capacity during 24-72 h culture with mitogens such as phytohemagglutinin (PHA), phorbol myristate acetate or concanavalin A. Stimulation of blood lymphocytes with endotoxins did not induce cell polarization in short-term but long-term culture resulted in an increase in the proportion of polarized cells that acquired locomotor morphologies. The majority of these cells were identified as esterase negative B-lymphocytes that migrated through filters. Despite the optimum time of incubation for each of these cell types being different, we found that lymphocytes respond to much lower concentrations of endotoxins than the neutrophils. These findings suggest that endotoxins of enteric pathogens modulate the functions of human blood neutrophils and lymphocytes.

• The Journal of Korean Medicine
• /
• v.20 no.1 s.37
• /
• pp.75-83
• /
• 1999

To investigate the effects of negative therapy at back meridian points on blood gas components and immune functions in male college students, this study was conducted on treatment types(abdomen group and back group) at three sampling times (before, post-2 wks and post-4 wks) by using $2{\times}3$ factoral design. Blood gas $components(pH,\;PCO_2,\;PO_2,\;HCO_3^-,\;O_2SAT,\;BE)$, red blood cell, hematocrit, hemoglobin, white blood cell and subsets(neutrophil, basophil, eosinophil. lymphocyte, monocyte), total T cells, helper T cells, suppressor T cells, Th/Ts ratio, total B cells, serum immunoglobulin levels (IgG, IgA, IgM, IgD, IgE), Cytokines(Interlukin$-1{\beta}$, -2, -4, 2 receptor, -6 and ${\gamma}$-interferon), NK cells were measured. Collected with data were analyzed statistically by repealed measured ANOVA. The pattern of change between two groups for hematocrit, hemoglobin, suppressor T cells, interleukin-6, ${\gamma}-interferon$, NK cells at post-2 weeks and BE, lymphocyte, basophil at post-4 weeks was significantly different(p<0.05) And also the pattern of change over time for ${HCO_3}^-$(2 wks vs 4 wks), WBC, neutrophil, lymphocyte(0 wks vs 2 wks and 2 wks vs 4 wks) was significantly different(p<0.05). In summary, these data suggest that negative therapy at back meridian points had an effect on blood gas components and immune functions in male college students because practicing negative therapy at back meridian points was not associated with changes of all blood gas components and immune factors but associated with changes of BE, hematocrit, hemoglobin, WBC. neutrophil, lymphocyte, interleukin-6. ${\gamma}-interferon$, NK cells.