Effects of Azelastine on Neutrophil Chemotaxis, Phagocytosis and Oxygen Radical Generation.

Akamatsu, Hirohiko; Asada, Yasuo; Niwa, Yukie

doi:10.1254/jjp.57.583

Cited by 13 publications

(8 citation statements)

References 30 publications

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“…These observations indicate that some cationic drugs reversibly inhibit membrane-bound enzymes or receptors. AZE may exert an anti-inflammatory action by inhibiting human PMNL phagocytosis as well as oxygen radical generation at the sites of inflammation [285,317].Antiallergic H 1 antihistamines AZE, KTF and OXA, were found to inhibit the superoxide generation of PMNL exposed to PMA in a whole-cell system. These results indicated that anti-allergic drugs with H 1 -receptor antagonism inhibited reconstitution of the solubilised membrane-bound enzyme and that they exerted a strong anti-inflammatory action [318,319].…”

Section: Ah and Reactive Oxygen Metabolites In Pmnlsmentioning

confidence: 99%

Antiplatelet and Antileukocyte Effects of Cardiovascular,Immunomodulatory and Chemotherapeutic Drugs

Nosáľ¹

2006

CHAMC

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In vitro and ex vivo interactions of betaadrenoceptor blocking drugs, antihistamines and chloroquine with blood platelets and polymorphonuclear leukocytes resulted in different alterations of regulatory functions of these blood cells. Inhibition of platelet aggregation, arachidonate regulatory pathway, 5-hydroxytryptamine transportation, removal of platelet membrane receptors, inhibition of second messenger pathways at subcellular level and suppression of phagocytosis are indicative of nonreceptor rather than specific receptor interactions. Binding of drugs with biomembranes is reversible depending on the ionic charge of the molecule and hydrophobicity of the bilayer, partition coefficient, pH and pKa of the amphiphilic molecules and other physico-chemical properties of amphiphilic drugs. Alterations in the drug molecule structure alters the drug-phospholipid binding profile. Any change in the metabolism of membrane phospholipids directly or indirectly influences one or more of the important components of the phospholipid-signalling pathway. In addition to changes in phospholipase A, C and D activities, protein kinase C, calmodulin-phosphodiesterase, Ca2+,Mg2+-ATPase, Na+,K+-ATPase and other messengers were found to be changed in cells and tissue after cationic amphiphilic drug (CAD) administration. Although not much has been understood of the mechanism by which some CAD affect immune functions, there are good reasons to suggest that these effects might occur. CADs share sufficient similarities in their structure even though they come from diverse pharmacological classes. CADs affect ion transport, immune functions, tumour growth, serotonin metabolism and several other functions in the body. Extensive therapeutic use and associated side effects have generated a great deal of interest in understanding the nonreceptor interactions with CADs.

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Section: Ah and Reactive Oxygen Metabolites In Pmnlsmentioning

confidence: 99%

Antiplatelet and Antileukocyte Effects of Cardiovascular,Immunomodulatory and Chemotherapeutic Drugs

Nosáľ¹

2006

CHAMC

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“…Kinetic studies demonstrated that the inhibitory effects of histamine on neutrophil function were only observed when histamine was added before N-fMLP and that inhibition occurred early in the sequence of neutrophil activation, did not persist after its removal and was reversed by the addition of cimetidine 10-20 s before stimulation with N-fMLP. Akamatsu et al (1991) studied the effects of azelastine (0.05, 0.5 or 5 mg·mL -1 ), an orally-active, selective histamine H1 receptor antagonist of the second-generation, on the production of ROS by human neutrophils. The ROS investigated were superoxide anion radical, hydrogen peroxide and hydroxyl radical.…”

Section: Oxidative Burst In Human Neutrophilsmentioning

confidence: 99%

“…In 1994, Ching et al (1994 showed that the histamine H2 receptor antagonists cimetidine, ranitidine and famotidine, besides affecting hydroxyl radicals, were also good hypochlorous acid scavengers. Akamatsu et al (1991) assessed the scavenging effects of azelastine on the ROS generated in a cellfree, xanthine-xanthine oxidase system. While azelastine significantly inhibited the generation of individual ROS, it did not markedly affect the ROS levels generated in this xanthine-xanthine oxidase system.…”

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confidence: 99%

Modulation of neutrophil oxidative burst via histamine receptors

Čı́ž

Lojek

2013

British J Pharmacology

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Histamine has the ability to influence the activity of immune cells including neutrophils and plays a pivotal role in inflammatory processes, which are a complex network of cellular and humoral events. One of the main functions manifested by activated neutrophils is oxidative burst, which is linked to the production of reactive oxygen species; therefore, the effects of histamine receptor agonists and antagonists on the oxidative burst of neutrophils is reviewed. A role for the well-characterized histamine H1 and H2 receptors in this process is discussed and compared to that of the recently discovered H4 receptor. LINKED ARTICLESThis article is part of a themed issue on Histamine Pharmacology Update. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2013.170.issue-1 AbbreviationsCaI, calcium ionophore A23187; N-fMLP, N-formyl-methionyl-leucyl-phenylalanine; OZP, opsonized zymosan particle; PMA, phorbol myristate acetate; ROS, reactive oxygen species; TLR, toll-like receptor Oxidative burst of neutrophilsNeutrophils are the most abundant type of white blood cells, comprising about 50-70% of all leukocytes. One of the most important defence mechanisms of neutrophils is associated with their ability to mediate a strong oxidative burst through the formation of reactive oxygen species (ROS). While oxidative burst is important for the elimination of invading microorganisms, the overproduction of ROS or the impairment of endogenous antioxidant defences may result in detrimental effects on the host's own cells and tissues (Freitas et al., 2009). Neutrophil oxidative burst is accompanied by the production of NADPH oxidase, which reduces oxygen to a superoxide anion radical. It is generally assumed that the NADPH oxidase is activated exclusively in the plasma membrane. However, in neutrophils, this assumption does not fit with the subcellular localization of the membrane components of the NADPH oxidase, which are stored in the granular compartments, and it has become increasingly evident that oxidants are also produced in an intracellular compartment, identified as specific granules. Myeloperoxidase is stored in another subset of granules, the azurophil granules, and participates in the processing of the ROS. In fact, it has been suggested that neutrophil activation is accompanied by the fusion of azurophil with specific granules, allowing these peroxidase-dependent reactions to take place (Karlsson and Dahlgren, 2002). PKC-d is required for full production of NADPH oxidase and activation of the respiratory burst. Neutrophils also express PKC-a and b, which may be involved in adhesion, degranulation and phagocytosis, but the evidence for this is not yet conclusive (Bertram and Ley, 2011). Although the complex mechanisms that coordinate the membrane traffic, oxidative burst and release of granule contents required for the microbicidal activities of neutrophils are not completely understood, it is evident that they are unique and differ from those in macrophages (Nordenfelt and Tapper, 2011). Neutr...

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“…Having said that, it is apparent that the majority of the second-generation antihistamines do have at least some inhibitory effects on mediator release from diverse cell types and that these appear to be independent of the potent H 1 blocking abilities of this class of compounds. Some examples of studies in which significant inhibitory effects on inflammatory cell function were observed with drug concentrations equal to or lower than the therapeutic plasma concentration include an inhibitory effect by azalastine on eosinophil superoxide radical production (67), while azalastine (68) and clemastine (69) inhibited generation of neutrophil superoxide radical. Terfenadine downregulated LTC 4 , LTCD 4 , TNF-␣ , and GM-CSF release from nasal polyp cells (70) and inhibited IgEdependent release of histamine and prostaglandin D 2 (PGD 2 ) from lung and skin mast cells (71).…”

Section: Anti-inflammatory Effects Of Antihistamines: In Vitro Studiesmentioning

confidence: 99%

The anti-inflammatory effects of the second-generation antihistamines

Walsh¹

2000

Dermatol Ther

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Second-generation histamines are widely used and effective drugs for the treatment of urticaria, atopic dermatitis, and in both seasonal and perennial allergic rhinitis. It has been recognized for some years that the newer antihistamines have a number of additional anti-inflammatory effects which appear to be independent of their H 1 receptor antagonist effect. These include in vitro inhibitory effects on eosinophil activation, chemotaxis, and on platelet, lymphocyte, or neutrophil activation, while in vivo several researchers have documented protective effects on the changes induced by skin prick test with histamine or allergen, in the specific nasal provocation test, and also limited protection to the specific bronchial provocation test. Other effects are inhibition of the accumulation of proinflammatory cells at allergen-challenged skin sites and downregulation of allergen-induced expression of the adhesion molecule ICAM-1 by epithelial cells. These additional properties may enhance the effects of these drugs in the treatment of allergic disease.

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Effects of Azelastine on Neutrophil Chemotaxis, Phagocytosis and Oxygen Radical Generation.

Cited by 13 publications

References 30 publications

Antiplatelet and Antileukocyte Effects of Cardiovascular,Immunomodulatory and Chemotherapeutic Drugs

Antiplatelet and Antileukocyte Effects of Cardiovascular,Immunomodulatory and Chemotherapeutic Drugs

Modulation of neutrophil oxidative burst via histamine receptors

The anti-inflammatory effects of the second-generation antihistamines

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