DIFFERENTIAL EFFECT OF HYDROCORTISONE ON EOSINOPHIL AND NEUTROPHIL PROLIFERATION
DIFFERENTIAL EFFECT OF HYDROCORTISONE ON EOSINOPHIL AND NEUTROPHIL PROLIFERATION
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DOI：
10.1172/jci112091
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发表时间：
1985-01-01
影响因子：
15.9
通讯作者：
ROSE, L
中科院分区：
文献类型：
--
作者：
BJORNSON, BH;HARVEY, JM;ROSE, L
糖皮质激素治疗导致循环中性粒细胞数量增加和嗜酸性粒细胞数量减少。利用双层软琼脂技术，我们研究了生理药理浓度的氢化可的松对人外周血和骨髓中性粒细胞祖细胞和嗜酸性粒细胞祖细胞增殖的影响。当研究外周血培养物时，用10-8-10-5 M氢化可的松琥珀酸盐以剂量反应方式抑制嗜酸性粒细胞增殖，并且包括49 ± 0.5M。4%的菌落培养，而只有4 . ±. 1%（P < 0.01）。另一方面，当向培养物中加入10-5 M氢化可的松时，中性粒细胞集落的数量增加了31%。为了使皮质类固醇发挥这种作用，有必要在培养开始后24小时内加入皮质类固醇。氢化可的松对粒细胞增殖的作用不能被结构类似的类固醇孕酮阻断。为了确定氢化可的松是直接作用于祖细胞还是通过效应细胞，研究了它对调节细胞群和刺激因子产生的作用。E-玫瑰花结细胞和/或粘附细胞的去除不影响嗜酸性粒细胞集落生长的抑制或中性粒细胞集落生长的增强。此外，添加有效的T细胞功能抑制剂环孢菌素A，未能影响嗜酸性粒细胞集落频率，这表明T细胞功能抑制不太可能解释所观察到的氢化可的松效应。白细胞条件培养基（LCM），来自与氢化可的松孵育的外周血单核细胞，是缺乏中性粒细胞和嗜酸性粒细胞集落刺激活性，而控制LCM刺激中性粒细胞和嗜酸性粒细胞增殖。这些数据表明，观察到的氢化可的松对粒细胞集落形成的影响不太可能是由中介介导的，氢化可的松直接作用于祖细胞。
Glucocorticosteroid therapy results in an increase in the number of circulating neutrophils and a decrease in the number of eosinophils. Utilizing the double layer soft agar technique, we examined the effect of physiologic to pharmacologic concentrations of hydrocortisone on the proliferation of human neutrophil progenitors and eosinophil progenitors from peripheral blood and bone marrow. When peripheral blood cultures were studied, eosinophil proliferation was inhibited in a dose-responsive fashion with 10-8-10-5 M hydrocortisone succinate, and comprised 49 .+-. 4% of the colonies cultures and only 4 .+-. 1% (P < 0.01) at pharmacologic levels of hydrocortisone (10-5 M). The number of neutrophil colonies, on the other hand, increased by 31% when 10-5 M hydrocortisone was added to cultures. In order for corticosteroids to exert this effect, it was necessary to add them within 24 h of the initiation of culture. The effect of hydrocortisone on granulocyte proliferation could not be blocked by progesterone, a structurally analogous steroid. To determine whether hydrocortisone was acting directly on the progenitor cell or via an effector cell, its effect on modulating cell populations and stimulating-factor production was studied. Removal of E-rosetting cells and/or adherent cells did not affect the inhibition of eosinophil colony growth or the enhancement of neutrophil colony growth. Furthermore, addition of the potent inhibitor of T cell function, cyclosporin A, failed to affect eosinophil colony frequency, suggesting that inhibition of T cell function was an unlikely explanation for the observed hydrocortisone effect. Leukocyte conditioned media (LCM), derived from peripheral blood mononuclear cells incubated with hydrocortisone, was devoid of both neutrophil and eosinophil colony-stimulating activity, whereas a control LCM stimulated both neutrophil and eosinophil proliferation. The data suggest that the observed hydrocortisone effect on granulocyte colony formation is unlikely to be mediated by an intermediary, and that hydrocortisone acts directly on progenitor cells.