• The Korean Journal of Pharmacology
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• v.24 no.1
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• pp.83-92
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• 1988

Although the release of lysosomal enzymes from activated PMN leukocyte can be regulated by intracellular cyclic nucleotide levels, other responses of PMN leukocyte according to the binding of neurotransmitters to either ${\beta}$-adrenergic or muscarinic receptors are still not clarified. In addition, the function of PMN leukocyte mediated by ${\alpha}$-adrenergic receptors is uncertain. Atropine, phentolamine and propranolol inhibited calcium uptake, superoxide generation, NADPH oxidase activity and phagocytic activity in activated PMN leukocyte, whereas carbachol and isoproterenol slightly further stimulated the responses of activated cells. Either carbachol or isoproterenol stimulated superoxide generation was inhibited by their antagonists, atropine and propranolol, respectively. The response of activated PMN leukocyte was inhibited by chlorpromazine, verapamil and dantrolene but slightly stimulated by lithium. On the other hand, chlorpromazine and dibucaine did not affect NADPH oxidase activity. Atropine, phentolamine and propranolol suppressed the calcium dependent phagocytic activity. Thus, the results suggest that atropine, phentolamine and propranolol may inhibit superoxide generation in activated PMN leukocyte by the inhibition of calcium influx and by their direct action on the NADPH oxidase system which is associated with autonomic receptors.

• The Korean Journal of Pharmacology
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• v.25 no.1
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• pp.75-85
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• 1989

In opsonized zymosan activated PMN leukocytes, N-ethylamleiamide and $Hg^{++}$, penetrable sulfhydryl group inhibitors, inhibited superoxide generation, NADPH oxidase activity and lysosomal enzyme (lactic dehydrogenase and ${\beta}-glucuronidase$) secretion. P-Chloromercuribenzoic acid and p-chloromercuribenzenesulfonic acid, surface sulfhydryl group inhibitors did not affect superoxide generation but effectively inhibited both NADPH oxidase activity and lysosomal enzyme secretion. During phagocytosis, contents of surface and soluble sulfhydryl groups were gradually decreased with increasing incubation times. N-ethylmaleiamide and $Hg^{++}$ caused a loss of both surface and soluble sulfhydryl groups. P-Chloromercuribenzoic acid and p-chloromercuribenzenesulfonic acid significantly decreased the surface sulfhydryl content but did not after soluble sulfhydryl groups. Cysteine and mercaptopropionylglycine inhibited superoxide generation and lysosomal enzyme secretion. Glutathione had no effect on superoxide generation but remarkably inhibited lactic dehydrogenase release. Suppression of superoxide generation by N-ethylmaleiamide was reversed by cysteine and mercaptopropionyl-glycine but not by glutathione. Inactivation of NADPH oxidase by N-ethylmaleiamide was prevented by glutathione, cysteine or mercaptopropionylglycine. Stimulated superoxide generaion by carbachol was completely abolished by N-ethylrnaleiamide and antagonized by atropine. Thus, the expression of PMN leukocyte response to external stimuli may be associated with the change of sulfhydryl groups content. It is suggested that lysosomal enzyme secretion is influenced by both surface and soluble sulfhydryl groups, whereas superoxide generation by intracellular soluble sulfhydryl groups.

• Restorative Dentistry and Endodontics
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• v.30 no.2
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• pp.138-144
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• 2005

This in vitro study monitored MMP-8 production on PMN by stimulated with the following three groups; Sonicated extracts of E. faecalis (SEF), SEF treated with $Ca(OH)_2$ (12.5mg/ml) for 7 days, and lipopolysac-charides(LPS) of E. coli. The level of MMP-8 in each group was immediately measured by ELISA. The data were analyzed with Kruskal-Wallis test and Mann-Whitney U test. In the SEF group, the level of production of MMP-8 was higher than the negative control group in low concentration ($0.05{\mu}g/ml$) of SEF (p < 0.05). but it decreased with an increase in the concentration of SEF (p < 0.05). In the case of SEF treated with $Ca(OH)_2$, all of the MMP levels were higher than negative control group (p < 0.05), but no statistical difference was found among the different SEF concentrations (p > 0.05). All of the levels in E. coli LPS were incresed with increasing concentrations (p < 0.05). According to this study we could summarized as follows: 1. MMP-8 was expressed at low level in untreated PMN group the levels of MMP-8 were upregulated in PMN stimulated by E. coli LPS groups. 2. In the SEF groups, the level of production of MMP-8 decreased with an increase in concentration of SEF (p < 0.05). So E. faecalis may have suppressive effect on the production of MMP-8 by PMN. 3. In the case of SEF treated with $Ca(OH)_2$, all of the MMP levels at different SEF concentrations were higher than untreated PMN group (p < 0.05), but no statistical difference was found among the different SEF concentrations (p > 0.05).

• Tuberculosis and Respiratory Diseases
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• v.39 no.3
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• pp.228-235
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• 1992

Background: Although polymorphonuclear leukocytes (PMN) are important in protecting the airways and alveolar surfaces, there is evidence that they can also injure the lung while exercising their defensive role. However it has been unclear whether PMN-induced pneumocyte injury is mediated by their direct cytotoxic effect on target cells or by PMN-derived cytotoxic mediators. On the other hand histamine was known not only to act as an important chemical mediator participated in the pathogenesis of some atotic and allegic disorders, but also to have an inhibitory effect on normal PMN functions. Method: To study the mechanism by which PMN induce pneumocyte injury, we cocultured PMN from four healthy nonsmokers or their PMN-derived supernatants (PMN-SPN) with monolayers of $^{51}Cr$-labeled human A549 pneumocytes and compared PMN-and PMN-SPN-mediated pneumocyte injuries measured by $^{51}Cr$ release assay. We also compared the effects of histamine on each pneumocyte injury. Results: 1) PMN-SPN showed more injurious effect on A549 pneumocytes than that of PMN itself regardless histamine pretreatment of PMN. 2) Pneumocyte injury by PMN with histamine pretreatment was increased or decreased compared with that by PMN without histamine pretreatment, according to histamine concentrations, and PMN stimulating agents and their concentrations. 3) Pneumocyte injury by PMN-SPN with histamine pretreatment tended to be decreased compared with that by PMN-SPN without histamine pretreatment. Conclusion: Our results suggest that PMN-SPN may play more important role in mediating pneumocyte injury than PMN itself and that histamine may partially play a protective role on PMN-induced pneumocyte injury. Alternatively we conclude that the effects of histamine on PMN-induced pneumocyte injury may be affected by microenvironment in vivo.

• Journal of Veterinary Clinics
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• v.23 no.4
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• pp.393-399
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• 2006

Ketamine, one of general anesthetics for human and veterinary use, is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist which interferes with the action of excitatory amino acids. It has been reported to impair various leukocyte functions. In this study, the effect of ketamine on the oxidative burst activity (OBA) of canine peripheral blood leukocytes was examined. The OBA of canine peripheral blood phagocytes was analyzed by flow cytometry system. Ketamine at higher concentration such as $1,000{\mu}M$ exhibited a low viability of leukocytes. Thus, ketamine was used at concentration of 10 to $500{\mu}M$ showing no cytotoxic effect and high cell viability. The OBA of leukocytes in the presence or absence of latex beads was analyzed by addition of dihydrorhodamine 123. The direct treatment of ketamine revealed the inhibitory effect on the OBA of peripheral blood polymorphonuclear cells (PMN) and monocyte-rich cells but not peripheral blood mononuclear cells (PBMC) in the presence of latex beads. However, when latex beads were not added to PMN, its OBA was not inhibited by ketamine. The OBA of PMN and monocyte-rich cells but not PBMC in the presence of latex beads was also inhibited by culture supernatant from ketamine-treated- PBMC but not -PMN. But the OBA of PMN in the absence of latex beads was not inhibited by culture supernatant from PBMC treated with ketamine. Therefore, these results suggested that ketamine has the inhibitory effect on the OBA of canine peripheral blood phagocytes such as neutrophils and monocytes during phagocytic response.

• Journal of Periodontal and Implant Science
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• v.25 no.2
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• pp.267-278
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• 1995

Human polymorphonuclear leukocytes(PMN) are the most numerous host cell in periodontal pockets and their presumed role is to form a protective barrier between the bacteria and periodontal tissues. Microbial component LPS activates macrophages to produce $IL-1{\beta}$, $MIP-1{\alpha}$, $-1{\beta}$, $TNF-{\alpha}$ and IL-6, etc. These cytokines have autocrine function to the macrophages, and paracrine function to other cell such as PMN and affect them to produce some biological functions. In the present study, human PMN were tested for the expression of $IL-1{\beta}$ and $MIP-1{\alpha}$ mRNA. Also we performed the receptor binding assay and in vitro assay for the antimicrobial action of HL-60 cell to determine whether HL-60 can replace the peripheral PMN in analyzing the biological functions. PMN were stimulated with $IL-1{\beta}$, TPA, $MIP-1{\alpha}$, LPS, IL-2 and total cytoplasmic RNA were extracted for the northern blot analysis. In order to determine the induction kinetics of $IL-1{\beta}$ or $MIP-1{\alpha}$ mRNA expression, cells were stimulated for 0,1,2,3 hours. We found peak expression of $IL-1{\beta}$ mRNA after 1hr of induction with $IL-1{\beta}$, LPS and after 2hr of induction with TPA. $MIP-l{\alpha}$ also induced but a scarce $IL-l{\beta}$ message from PMN. In contrast to the $IL-l{\beta}$ mRNA expression, $MIP-1{\alpha}$ were not induced from PMN in any culture conditions. Receptors for $MIP-1{\alpha}$ were identified on dibutyryl cyclic AMP(dbcAMP)-treated HL-60 as well as peripheral PMN. dbcAMP treatment significantly enhanced antimicrobial action of undifferentiated HL-60 cell. MIP-1 further increased enhancing effect of dbcAMP. $IL-1{\beta}$, to a lesser extent, also increased dbcAMP-induced enhancing effect of antimicrobial action of HL-60 cell.

• Biomedical Science Letters
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• v.27 no.1
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• pp.19-27
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• 2021

This study was undertaken to clarify the effects of omega-3 fatty acid on endotoxin-induced acute lung injury. Rabbits were randomly assigned to one of four groups. Each group received intravenous infusion of saline only, saline and Escherichia coli endotoxin, omegaven infuison (0.5 mL/kg/hr) and endotoxin, lipoven (0.5 mL/kg/hr) and endotoxin respectively. Infusion of saline was started 0.5 hr before the infusion of saline or endotoxin, and omegaven and lipoven were started 2 hours after endotoxin infusion for 4 hours. The lungs of rabbits were ventilated with 40% oxygen. Mean blood pressure, heart rate, arterial oxygen tension (PaO2), and peripheral blood leukocyte were recorded. The wet/dry (W/D) weight ratio of lung and lung injury score were measured, and analysis of bronchoalveolar lavage fluid (BALF) was done. Endotoxin decreased PaO2, and peripheral blood leukocyte and platelet count. And it increased W/D ratio of lung, lung injury score and leukocyte count, percentage of PMN cells, concentration of IL-8 in BALF. Omegaven attenuated all these changes except for peripheral blood leukocyte counts. Omegaven attenuated endotoxin-induced acute lung injury in rabbits mainly by inhibiting neutrophil and IL-8 responses, which may play a central role in endotoxin-related lung injury.

• Journal of Periodontal and Implant Science
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• v.25 no.3
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• pp.733-740
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• 1995

This investigation was undertaken to determine the relationship between the amount of polymorphonuclear leukocyte(PMN) enzyme myeloperoxidase(MPO) in gingival crevicular fluid(GCF) collected from active or control site and gingival disease status described by clinical indices(gingival index, papillary bleeding index, pocket depth, periotron unit). The results were as follows : 1. MPO activity/site was greater at active sites than at control sites. 2. According to increasing the clinical parameters, MPO/sites was higher statistically (P<0. 01, P<0.05). 3. High MPO(unit/site) groups was higher statistically than low MPO(unit/site) groups in various clinical parameters. 4. Correlation coefficients between MPO(unit/site) and GI, MPO($unit/{\mu}l$ GCF) and periotron unit were 0.4782, -0.5901, respectively.

• The Korean Journal of Physiology and Pharmacology
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• v.8 no.6
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• pp.319-327
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• 2004

This study was aimed at evaluating the effect of defibrotide on the development of the surgically induced reflux esophagitis, on gastric secretion, lipid peroxidation, polymorphonuclear leukocytes (PMNs) accumulation, polymorphonuclear leukocytes adherence, superoxide anion and hydrogen peroxide production in PMNs, scavenge of hydroxyl radical and hydrogen peroxide, cytokine (interleukin-1 ${\beta}$, tumor necrosis $factor-{\alpha}$) production in blood, and intracelluar calcium mobilization in PMNs. Defibrotide did not inhibit the gastric secretion and not change the gastric pH. Treatment of esophagitis rats with defibrotide inhibited lipid peroxidation, and myeloperoxidase (MPO) in the esophagus in comparison with untreated rats. Defibrotide significantly decreased the PMN adherence to superior mesenteric artery endothelium in a dose-dependent manner, Superoxide anion and hydrogen peroxide production in $1{\mu}M$ formylmethionylleucylphenylalanine (fMLP)- or $0.1{\mu}g/ml$ N-phorbol 12-myristate 13-acetate (PMA)-activated PMNs was inhibited by defibrotide in a dose-dependent fashion. Defibrotide effectively scavenged the hydrogen peroxide but did not scavenge the hydroxyl radical. Treatment of esophagitis rats with defibrotide inhibited interleukin-1 ${\beta}$ production in the blood in comparison with untreated rats, but tumor necrosis $factor-{\alpha}$ production was not affected by defibrotide. The fMLP-induced elevation of intracellular calcium in PMNs was inhibited by defibrotide. The results of this study suggest that defibrotide may have partly beneficial protective effects against reflux esophagitis by the inhibition lipid peroxidation, PMNs accumulation, PMNs adherence to endothelium, reactive oxygen species production in PMNs, inflammatory cytokine production(i.e. interleukin-1 ${\beta}$), and intracellular calcium mobilization in PMNs in rats.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.2
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• pp.403-411
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• 2003

For evaluating the effect of Siegesbeckiae Herba (here after abbreviated as SBH) on rheumatoid arthritis, the experiment was carried out; Incidence of rheumatoid arthritis, IRA(indices of rheumatoid arthritis), immunophenotypes by flow cytometer and histopathological changes in MRL/MpJ-Ipr-Ipr Mice in vivo were studied. The results were obtained as follows: 1. Incidence of RA in MRL/Ipr mice was suppressed to 60% of control by SBH. 2. IRA was significantly reduced for IgG3 and IgM at 20 weeks of age and for IgG2b at 12 and 20 weeks of age in mice by SBH compared with control. 3. Immunophenotypes such as CD4/sup +//CD25/sup +/, CD8/sup +//CD3e/sup +/, CD69/sup +//B220/sup +/, NK/sup +//CD3e/sup +/ were significantly increased by SBH compared with control. 4. In histopathological analysis, SBH suppressed the progression of PMN(polymorphonuciear leukocyte), leukocyte and fibroblast infiltration, and subsynovial soft tissue edema frequently showing in the early stage of the arthritis, and also effectively reduced the degeneration of cartilages and degenerative bone symptoms. These results suggest Siegesbeckiae Herba can be effectively applied to the treatment of rheumatoid arthritis and it is still necessary to isolate effective compound from Siegesbeckiae Herba in the near future.