Ryosuke Eda

Effect of cetirizine on human eosinophil superoxide generation, eosinophil chemotaxis and eosinophil peroxidase in vitro

Cetirizine, a potent H1-antagonist, has been reported to inhibit eosinophil migration into human skin. We, therefore, further evaluated the effect of cetirizine on eosinophil function, including superoxide anion generation, chemotaxis, and eosinophil peroxidase (EP) release. In allergic subjects, superoxide anion generation 60 min after platelet-activating factor (PAF) activation was inhibited by concentrations of cetirizine ranging from 0.01 to 1 microgram/ml (2.612 x 10(-8) to 2.612 x 10(-6) M). No significant inhibition was observed in normal subjects. PAF (10(-6) M)-induced eosinophil chemotaxis was also inhibited by cetirizine. In allergic subjects, percent inhibitions were 47.5 +/- 6.1% at 0.01 microgram/ml, 50.8 +/- 5.1% at 0.1 microgram/ml and 58.9 +/- 6.4% at 1 microgram/ml of cetirizine. In allergic subjects, N-formyl-methionyl-lencyl-phenylalanine induced eosinophil chemotaxis was inhibited by cetirizine, although EP release was not. These results suggest cetirizine has effects on eosinophils which can not be explained by H1-blockade alone.

Inhibitory effects of formoterol on platelet-activating factor induced eosinophil chemotaxis and degranulation.

A new long-acting beta 2-agonist, formoterol, has been reported to have a greater efficacy and duration of action in asthmatic patients as compared to conventional beta 2-agonists. We recently demonstrated that formoterol inhibited antigen-induced late asthmatic response (LAR) and accompanying airway eosinophilia in guinea pigs. In this study, we investigated the direct effect of formoterol in vitro on human eosinophil function, focusing on platelet-activating factor (PAF)-induced eosinophil chemotaxis and eosinophil cationic protein (ECP) release. Purified normodense eosinophils were separated by discontinuous gradient from 12 mild asthmatic patients. Formoterol in concentrations of 1-100 microM significantly inhibited PAF-induced eosinophil chemotaxis in a dose-dependent manner with a concentration of drug required to produce 50% inhibition (IC50) of 10.16 microM; % inhibition: 22.9 +/- 13.0% (1 microM), 51.6 +/- 12.7% (10 microM), 75.0 +/- 11.3% (100 microM). When formyl-methionyl-leucyl-phenylamine (FMLP) was used as a chemoattractant, a similar inhibition of eosinophil chemotaxis by formoterol was observed; % inhibition: 13.1 +/- 5.0% (1 microM). 47.7 +/- 7.6% (10 microM), 65.5 +/- 16.5% (100 microM). A conventional beta 2-agonist, salbutamol, at doses to 100 microM did not show any inhibitory effects on PAF-induced eosinophil chemotaxis. Formoterol in concentrations of 1-100 microM also significantly inhibited PAF-induced ECP release from eosinophils; % inhibition: 21.7 +/- 9.0% (1 microM), 39.3 +/- 7.4% (10 microM), 39.6 +/- 8.4% (100 microM). In the presence of phosphodiesterase inhibitors, theophylline or isobutylmethyl xanthine (IBMX), the inhibition by formoterol on PAF-induced ECP release was enhanced.(ABSTRACT TRUNCATED AT 250 WORDS)

Eosinophil Accumulation and Activation in Antigen-Induced Late Asthmatic Response in Guinea Pigs

The purpose of this study was to investigate the participation of airway eosinophils in the antigen-induced late asthmatic response (LAR) and increased airway responsiveness in the guinea pig model of asthma. After antigen challenge, guinea pigs sensitized with aerosolized ovalbumin showed a late-phase decrease in specific airway conductance, which was accompanied by airway hyperresponsiveness to histamine, eosinophilia in the bronchoalveolar lavage fluid (BALF), decreased BALF eosinophil density, and increased generation of superoxide anions from purified BALF eosinophils. We demonstrated an association of the LAR with eosinophil accumulation and activation in the airway.

Attenuation of antigen-induced bronchoconstriction in guinea pigs by a New Xanthine derivative (HWA448)

We examined the effect of a new xanthine derivative, HWA448, on antigen-induced bronchoconstriction in actively sensitized guinea pigs. Guinea pigs were sensitized by intraperitoneal injection of bovine serum albumin (BSA) on two occasions, separated by 10 days. Two weeks after the second injection, the animal was placed in a two-chambered whole body plethysmograph and specific airway resistance (SRaw) was monitored for 10 min after an aerosol inhalation of BSA. HWA448 prevented the increase in SRaw after challenge (at 5 and 20 mg/kg i.p.). Aminophylline also prevented the increase in SRaw at 20 mg/kg, but not at a 5-mg/kg dose. The concentration of HWA448, which produced 50% relaxation of the tracheal rings constricted with 0.1 mM of histamine, was 49.9 microM as compared with 18.2 microM in aminophylline. HWA448 has a protective effect on antigen-induced bronchoconstriction in guinea pigs and may be a useful agent in the therapy of bronchial asthma.