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Suppression of respiratory burst of polymorphonuclear leukocytes by azelastine hydrochloride (Azeptin).

Abstract：

:The inhibitory action of azelastine hydrochloride (Azeptin) on the respiratory burst in peripheral polymorphonuclear leukocytes (PMN) and pulmonary alveolar macrophages (PAM) has been studied. Azeptin in vitro suppressed chemiluminescence and superoxide (O2-) generation by human PMN in a dose- and time-dependent manner. Phorbol myristyl acetate (PMA) and formyl-methionyl-leucyl-phenylalanine (FMLP)-induced O2- generation were strongly suppressed by 10(-6) M and 10(-5) M Azeptin, respectively. PMN and PAM from rabbits injected with Azeptin 0.2 mg.kg-1 for 5 days showed lower chemiluminescence and O2- generation than cells from untreated rabbits. Nitroblue tetrazolium reduction activity in human PMN was suppressed by treatment of PMN with 10(-6) M Azeptin for 6 h. Inositol trisphosphate, intracellular free calcium, and protein kinase C activity were decreased by 10(-6) M to 10(-5) M Azeptin. The tyrosine phosphorylation of many proteins, especially a 115 kDa protein, was suppressed by 10(-5) M Azeptin. However, superoxide dismutase activity in PMN, PAM, and lung tissue samples was only slightly decreased, even when the rabbits were treated with 1.0 mg.kg-1 Azeptin for 5 days. The results suggest that Azeptin suppresses multiple signal transduction steps in the respiratory burst of PMN. This suppressive action should be very useful in the prevention and treatment of reactive oxygen-associated disorders.

journal_name

Eur J Clin Pharmacol

journal_title

European journal of clinical pharmacology

authors

Ueta E,Osaki T,Kawasaki N,Nomura Y

doi

10.1007/BF00194963

subject

Has Abstract

pub_date

1994-01-01 00:00:00

pages

139-45

issue

2

eissn

0031-6970

issn

1432-1041

journal_volume

47

pub_type

杂志文章

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