No abstract

Cetirizine, a potent Hrantagonist, 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 μg/ml (2.612 × 10^––8 to 2.612 × 10^––6M). No significant inhibition was observed in normal subjects. PAF (10^––6M)-induced eosinophil chemotaxis was also inhibited by cetirizine. In allergic subjects, percent inhibitions were 47.5 ± 6.1% at 0.01 μg/ml, 50.8 ± 5.1% at 0.1 μg/ml and 58.9 ± 6.4% at 1 μg/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.

We previously reported a significant decrease in neutrophils at 5 min and an increased number of neutrophils at 15 min after PAF-acether inhalation. To investigate the mechanism, we measured the neutrophil chemotactic activity of the sera. Neutrophil chemotactic activity (NCA) of the serum at 5 min was greater than at baseline (p < 0.01) or at 15 min (p < 0.05). Furthermore, we investigated the correlation between the change in NCA and decreased number of neutrophils. A significant correlation was found between these two at 5 min (r = 0.751 p < 0.05). These data suggest that an elevation of NCA may play an important role in the decrease of circulating neutrophils after PAF-acether inhalation.

We investigated the density distribution of neutrophils in peripheral blood of allergic subjects. We divided neutrophils into four groups: fraction 1 (density > 1.085), fraction 2 (1.081 < density ≤ 1.085), fraction 3 (1.077 < density ≤ 1.081) and fraction 4 (density ≤ 1.077). The percentage of neutrophils in fraction 2 in allergic rhinitis (AR) subjects or asthmatics was lower than that in normals (p < 0.01). The percentage of neutrophils in fraction 3 and fraction 4 from AR or asthmatics was greater than that in normals (fraction 3, p < 0.01; fraction 4, p < 0.05). In neutrophils from AR subjects (fraction 3), chemotaxis to N-formyl-methionyl-leucyl-phenylalanine or platelet-activating factor (PAF) was enhanced compared to fraction 2. PAF (10^––7M) changed the density of neutrophils (p < 0.01), which were inhibited by WEB 2086 (p < 0.05). Furthermore, granulocyte-macrophage colony-stimulating factor changed the density of neutrophils (p < 0.01). These findings suggest that biological agents may activate neutrophils and convert their density resulting in neutrophils with lower density in allergic subjects.

Eosinophils play a major role in the pathogenesis of bronchial asthma. In this study, we examined the density characteristics of blood eosinophils from 9 normal healthy individuals and 9 allergic asthmatic patients. Furthermore, the effect of platelet-activating factor, a potent mediator of inflammation, and calcium ionophore, A23187, on the density of normodense eosinophils (density > 1.085 g/ml) has also been examined. Initially, asthmatic patients had 27.0 +/- 1.1% eosinophils of lighter density (density < or = 1.081 g/ml), significantly greater than that in the normal individuals (7.5 +/- 0.5%). After exposure to platelet-activating factor (1 microM) or calcium ionophore (A23187, 1 microgram/ml), the normodense eosinophils switched to hypodense in both groups: 16.7 +/- 2.1% and 54.2 +/- 3.7%, respectively, in normal individuals, and 30.6 +/- 5.7% and 77.4 +/- 2.3%, respectively, in asthmatic patients. These data demonstrated that a certain percentage of normodense eosinophils from asthmatics and normal subjects switched to hypodense after activation with platelet-activating factor or calcium ionophore. Furthermore, eosinophils from asthmatics switched to a greater degree than in normal subjects, suggesting that the normodense eosinophils in asthmatics become primed probably by endogenously released mediators.