Inhibitory effects of various drugs on phorbol myristate acetate and n−-formyl methionyl leucyl phenylalanine induced O2− production in polymorphonuclear leukocytes

Taniguchi, Katsuhiko; Takanaka, Koichiro

doi:10.1016/0006-2952(84)90072-8

Cited by 43 publications

(18 citation statements)

References 32 publications

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“…Several authors have investigated the effects of various antiasthma drugs including antiallergic drugs, P-adrenergic agonists and corticosteroids on the in vitro generation of 03 and other active oxygen species from PMNs or alveolar macrophages employing a va riety of methods [24][25][26][27][28][29][30][31][32], In the present study, we ex amined the effects of some antiasthma drugs on the in vitro generation of O5 in PMNs from asthmatic pa tients using MCLA as a highly sensitive and specific CL probe for Oi.…”

Section: Discussionmentioning

confidence: 99%

Effects of Antiasthma Drugs on Superoxide Anion Generation from Human Polymorphonuclear Leukocytes or Hypoxanthine-Xanthine Oxidase System

Katô

Morikawa²,

Kimura³

et al. 1991

Int Arch Allergy Immunol

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Airway inflammation with human polymorphonuclear leukocytes (PMNs) may play an important role in the pathophysiology of bronchial asthma. Superoxide anion (O₂^––) and other active oxygen species derived from PMNs cause tissue damage. To evaluate the effects of antiasthma drugs on airway inflammation or antioxidative actions due to the inhibition of O₂^–– generation, we investigated the effects of antiallergic drugs, β-adrenergic agonists, theophylline and corticosteroids, on the in vitro generation of O₂^–– by human PMNs, using a chemiluminescence (CL) method dependent on a Cypridina luciferin analog (MCLA), a highly sensitive and specific CL probe for O₂^––. We found that azelastine, one of the antiallergic drugs, and isoproterenol inhibited FMLP-induced O₂^–– generation in a dose-dependent fashion, whereas the other drugs exhibited no such inhibitory action except at very high concentrations. Furthermore, we found that isoproterenol inhibited O₂generation from the hypoxanthine-xanthine oxidase system (an O₂^––-generating system) in a dose-dependent fashion, unlike azelastine and the other drugs. These results suggest that azelastine and isoproterenol inhibit the process of O₂^–– generation from PMNs, while isoproterenol also scavenges O₂^––. These drugs may be beneficial in the treatment of airway inflammation due to O₂^–– generation in bronchial asthma.

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Section: Discussionmentioning

confidence: 99%

Effects of Antiasthma Drugs on Superoxide Anion Generation from Human Polymorphonuclear Leukocytes or Hypoxanthine-Xanthine Oxidase System

Katô

Morikawa²,

Kimura³

et al. 1991

Int Arch Allergy Immunol

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“…On the other hand, the acidic agents were developed on the basis of ob servations that DSCG (disodium cromogly cate), bicalein and caffeic acid are inhibitors of chemical mediator release (12,15). We have previously shown that superoxide generation, arachidonic acid release as well as changes of membrane potential were sup pressed by one of the basic antiallergic agents, azelastine (16)(17)(18). In this study, we attemped to compare the inhibitory effects of antial lergic drugs on the release of arachidonic acid, leukotriene B4 and superoxide from ac tivated human neutrophils to clarify the action sites of the various basic and acidic anti allergic drugs.…”

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confidence: 99%

Action sites of antiallergic drugs on human neutrophils.

1990

Self Cite

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Abstract-Sites of the inhibitory action of antiallergic drugs (azelastine, oxatomide, tranilast, repirinast and amlexanox) on human neutrophils were investigated by measuring leukotriene B4 formation, arachidonic acid release and superoxide generation. Results obtained in this study were as follows: (1) Formations of leukotriene B4 by neutrophils activated with a calcium ionophore (A23187) were effectively inhibited by all types of antiallergic drugs examined here, although the required concentrations were within a range of 20-200 /tM. (ii) Releases of arachidonic acid from activated cells were diminished by azelastine and oxatomide that were classified as basic antiallergic drugs. On the contrary, acidic antiallergic agents including repirinast, amlexanox and tranilast enhanced the arachidonic acid liberation. (iii) Generations of superoxide from neutrophils activated with either phorbol 12-myristate 13-acetate or n-formyl-methionyl-leucyl-phenylalanine were effectively diminished only by the basic antiallergic drugs.

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“…It has been established that INDO inhibits cycloox ygenase and various lipoxygenases [2,3], and that PMNs are an important source of arachidonate metabolites in acute inflammation [4]. Furthermore, many studies have demon strated that this drug can modulate the activ ity of PMNs in vivo and in vitro [5][6][7], INDO also accumulates in vivo in inflamed areas and acidic tissues [8][9][10]. Only few studies [11][12][13][14] have examined the association of non steroidal anti-inflammatory drugs (NSAIDs) with PMNs and none to date have examined the molecular interaction of INDO with PMNs.…”

Section: Introductionmentioning

confidence: 99%

Modes of Association of Indometacin with Human Polymorphonuclear Leucocytes

Raghoebar¹,

Tiemessen²,

Berg

et al. 1989

Pharmacology

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The basic transport properties of indometacin (INDO) were investigated in human blood polymorphonuclear leucocytes (PMNs) of healthy volunteers. The silicone oil cushion centrifugation method was used as ligand-binding assay for both the measurements of the cellular association of INDO and the intracellular volume. This assay enabled us to calculate the intracellular INDO concentrations. A considerable amount of INDO accumulates in the PMNs to cause cell/medium ratios between 20 and 90. At low INDO levels (1–10 nmol/l) the cell/medium ratio appeared to be higher than at high INDO levels (>2 μmol/l). This finding suggests that the cell accumulation of INDO comprises saturable binding and/or transport components. Scatchard analysis of the association isotherm of INDO after incubation for 60 min at 37 °C reveals apparent K_D values of 3.7 μmol/l (low affinity) and 1.2 nmol/l (high affinity). The number of high-affinity association sites (60 fmol/3 × 106 PMNs) was 1,000–2,000 times lower than the number of low-affinity association sites (103 pmol/3 × 10⁶ PMNs). INDO cell association is suggested to be a net result of diffusive and mediated influx and efflux mechanisms, and of binding to (plasma) membranes. The capacity of the PMN to accumulate INDO is enhanced upon (1) establishment of an inward gradient of [H⁺], and (2) activation of the Na⁺-H⁺ antiport by chemotactic peptide. The possible mechanisms of incorporation of INDO in the PMN are discussed in the scope of the proposed PMN-related anti-inflammatory action of INDO.

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Inhibitory effects of various drugs on phorbol myristate acetate and n−-formyl methionyl leucyl phenylalanine induced O2− production in polymorphonuclear leukocytes

Cited by 43 publications

References 32 publications

Effects of Antiasthma Drugs on Superoxide Anion Generation from Human Polymorphonuclear Leukocytes or Hypoxanthine-Xanthine Oxidase System

Effects of Antiasthma Drugs on Superoxide Anion Generation from Human Polymorphonuclear Leukocytes or Hypoxanthine-Xanthine Oxidase System

Action sites of antiallergic drugs on human neutrophils.

Modes of Association of Indometacin with Human Polymorphonuclear Leucocytes

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