BLOOD AND BRONCHOALVEOLAR EOSINOPHILS IN ALLERGIC SUBJECTS AFTER SEGMENTAL ANTIGEN CHALLENGE - SURFACE PHENOTYPE, DENSITY HETEROGENEITY, AND PROSTANOID PRODUCTION
BLOOD AND BRONCHOALVEOLAR EOSINOPHILS IN ALLERGIC SUBJECTS AFTER SEGMENTAL ANTIGEN CHALLENGE - SURFACE PHENOTYPE, DENSITY HETEROGENEITY, AND PROSTANOID PRODUCTION
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DOI：
10.1016/0091-6749(94)90252-6
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发表时间：
1994-04-01
影响因子：
14.2
通讯作者：
BOCHNER, BS
中科院分区：
文献类型：
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作者：
KROEGEL, C;LIU, MC;BOCHNER, BS
嗜酸性粒细胞浸润到气道中与哮喘的病理生理学有关。为了提高我们对嗜酸性粒细胞在哮喘中的功能的理解，我们比较了嗜酸性粒细胞的表型和功能，同时从血液和支气管肺泡灌洗（BAL）的过敏受试者肺节段性变应原激发后19小时。采用不连续密度梯度离心法纯化嗜酸性粒细胞，并对其在各层的分布进行定量。通过免疫荧光和流式细胞术分析来自血液和BAL（纯度> 70%）的1.080至1.085 gm/ml界面处的嗜酸性粒细胞的几种表面标志物，包括粘附活化抗原。与对照稀释液激发的BAL部位相比，抗原激发部位的BAL中嗜酸性粒细胞显著增加（0.3% +/- 1% vs 28.1% +/-9.7%，n = 12，p < 0.002），低密度（比重< 1.080 gm/ml）的百分比高于外周血（51.3 +/- 5.3 vs 19.0 +/- 4.4，n = 15，p < 0.01）。在体外，静息和活化的BAL嗜酸性粒细胞生物合成血栓素B-2比血液嗜酸性粒细胞少。尽管BAL和血液嗜酸性粒细胞表达相似水平的Fc γ RII（CD 32）、CD 11 a和CD 45，但BAL嗜酸性粒细胞上Mo-1（CD 11b）的静息水平上调（血液嗜酸性粒细胞的平均荧光强度为316% +/- 48%，n = 5，p < 0.05）。用1 μ mol/L血小板活化因子或N-甲酰-甲硫氨酰-亮氨酰-苯丙氨酸体外刺激的血嗜酸性粒细胞达到与BAL嗜酸性粒细胞相似的CD 11b表达水平。相反，BAL嗜酸性粒细胞上的CD 11b表达不能进一步增加。这些结果证实了下气道的抗原激发促进了肺中的嗜酸性粒细胞浸润。由于这些嗜酸性粒细胞的密度较低，表达最大量的CD 11b，并且比外周血嗜酸性粒细胞的反应性低，我们得出结论，嗜酸性粒细胞在此募集过程中经历活化，随后可能是反应性降低的状态。
Eosinophil infiltration into the airways has been implicated in the pathophysiology of asthma. To improve our understanding of the function of eosinophils in asthma, we have compared the phenotype and function of eosinophils obtained simultaneously from blood and bronchoalveolar lavage (BAL) of allergic subjects 19 hours after segmental lung allergen challenge. Eosinophils were purified by discontinuous density gradient centrifugation, and their distribution at various layers was quantitated. Eosinophils at the 1.080 to 1.085 gm/ml interfaces from blood and BAL (purity > 70%) were analyzed by immunofluorescence and flow cytometry for several surface markers including adhesion-activation antigens. Eosinophils in BAL from antigen-challenged sites were markedly increased compared with control diluent-challenged BAL sites (0.3% +/- 1% vs 28.1% +/- 9.7%, n = 12, p < 0.002), and a greater percentage were hypodense (specific gravity < 1.080 gm/ml) than in peripheral blood (51.3 +/- 5.3 vs 19.0 +/- 4.4, n = 15, p < 0.01). In vitro, resting and activated BAL eosinophils biosynthesized less thromboxane B-2 than blood eosinophils. Although both BAL and blood eosinophils expressed similar levels of Fc gamma RII (CD32), CD11a, and CD45, resting levels of Mo-1 (CD11b) were upregulated on BAL eosinophils (mean fluorescence intensity 316% +/- 48% of blood eosinophils, n = 5, p < 0.05). Blood eosinophils stimulated in vitro with 1 mu mol/L platelet activating factor or N-formyl-methionyl-leucyl-phenylalanine achieved levels of CD11b expression similar to those of BAL eosinophils. In contrast, CD11b expression on BAL eosinophils could not be further increased. These results confirm that antigen challenge of the lower airways promotes eosinophil infiltration in the lung. Because these eosinophils are of lower density express maximal amounts of CD11b, and are less responsive than peripheral blood eosinophils, we conclude that eosinophils undergo activation during this recruitment process, which may be followed by a state of decreased responsiveness.