Spoelstra F M, Berends C, Dijkhuizen B, de Monchy J G, Kauffman H F
Dept of Allergology, University Hospital Groningen, The Netherlands.
Eur Respir J. 1998 Sep;12(3):585-91. doi: 10.1183/09031936.98.12030585.
The nonspecific phosphodiesterase inhibitor theophylline, widely used in asthma therapy, may cause a decrease in inflammatory responses of airways. In asthma, eosinophils migrate to the airway wall and become activated. Activated eosinophils are characterized by low cell density, as well as increased expression of CD11b and reduced expression of L-selectin, two adhesion molecules involved in transendothelial migration. To study the anti-inflammatory effect of theophylline on granulocyte adhesion molecules in vitro, the platelet-activating factor (PAF)-induced density shift was determined by density centrifugation and the modulation of CD11b and L-selectin expression by flow cytometry on eosinophils and neutrophils in human whole blood. A relatively high concentration of theophylline (10(-3) M) inhibited the increase in the percentage of hypodense eosinophils and neutrophils in whole-blood samples after PAF stimulation in vitro. A more pharmacological concentration (10(-4) M) inhibited the CD11b upregulation and L-selectin shedding induced by PAF (10(-7) M) on both eosinophils and neutrophils. The effect of isoproterenol on the inhibitory effect of theophylline was mainly additive, but a small synergistic effect could not be excluded. In conclusion theophylline can attenuate eosinophil and neutrophil activation in vitro at the level of adhesion molecule expression and changes in cell density. This may have implications for transendothelial migration of these cells in asthma.
非特异性磷酸二酯酶抑制剂茶碱广泛应用于哮喘治疗，可能会导致气道炎症反应减弱。在哮喘中，嗜酸性粒细胞迁移至气道壁并被激活。活化的嗜酸性粒细胞具有细胞密度低以及CD11b表达增加和L-选择素表达减少的特征，这两种黏附分子参与跨内皮迁移。为了在体外研究茶碱对粒细胞黏附分子的抗炎作用，通过密度离心法测定血小板活化因子（PAF）诱导的密度变化，并采用流式细胞术检测茶碱对人全血中嗜酸性粒细胞和中性粒细胞CD11b和L-选择素表达的调节作用。相对高浓度的茶碱（10⁻³ M）可抑制体外PAF刺激后人全血样本中低密度嗜酸性粒细胞和中性粒细胞百分比的增加。更具药理学意义的浓度（10⁻⁴ M）可抑制PAF（10⁻⁷ M）诱导的嗜酸性粒细胞和中性粒细胞CD11b上调和L-选择素脱落。异丙肾上腺素对茶碱抑制作用的影响主要是相加性的，但不能排除有小的协同作用。总之，茶碱可在体外黏附分子表达和细胞密度变化水平上减弱嗜酸性粒细胞和中性粒细胞的活化。这可能对这些细胞在哮喘中的跨内皮迁移有影响。
