Sorden S D, Lemanske R F, Castleman W L
Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison.
Vet Pathol. 1990 Jul;27(4):217-22. doi: 10.1177/030098589002700401.
Airway eosinophilia has been proposed as a major pathogenetic event in bronchial asthma and airway hyperresponsiveness. Intravenous injection of Sephadex G200 in rats induces pulmonary and blood eosinophilia and alters pulmonary responsiveness to 5-hydroxytryptamine. To characterize the early pulmonary inflammatory responses following Sephadex administration, and to determine the timing of the onset of pulmonary eosinophilia relative to blood eosinophilia, Sprague-Dawley rats were injected intravenously with Sephadex G200 beads. Lungs and other tissues were examined by light and transmission electron microscopy at 4, 12, 24, 48, 72, and 96 hours after injection. Blood eosinophil counts were determined at 0, 24, and 96 hours after injection. Sephadex beads were trapped initially in small caliber muscular pulmonary arteries associated with terminal bronchioles and in intra-acinar locations. There was marked infiltration of eosinophils and macrophages around the beads and into arterial walls and edematous periarterial and peribronchiolar connective tissue as early as 4 hours after injection. Periarterial-peribronchiolar eosinophil aggregates peaked in density at 24 and 48 hours. Macrophages and multinucleated cells dominated the inflammatory cell responses in arteries immediately surrounding partially degraded Sephadex beads from 24 to 96 hours. Bone marrow eosinophilopoiesis and blood eosinophilia were not detected until 96 hours. We conclude that Sephadex induces pulmonary eosinophilia prior to blood eosinophilia and suggest that Sephadex may induce pulmonary release of one or more eosinophil chemotactic substance(s). This model may prove useful in the study of factors that influence eosinophil migration into the lung in various disease states.
气道嗜酸性粒细胞增多被认为是支气管哮喘和气道高反应性的主要发病机制。给大鼠静脉注射葡聚糖G200可诱导肺部和血液嗜酸性粒细胞增多，并改变肺对5-羟色胺的反应性。为了描述葡聚糖给药后早期肺部炎症反应的特征，并确定肺部嗜酸性粒细胞增多相对于血液嗜酸性粒细胞增多的起始时间，给Sprague-Dawley大鼠静脉注射葡聚糖G200珠。在注射后4、12、24、48、72和96小时，通过光镜和透射电子显微镜检查肺和其他组织。在注射后0、24和96小时测定血液嗜酸性粒细胞计数。葡聚糖珠最初被困在与终末细支气管相关的小口径肌性肺动脉和腺泡内位置。早在注射后4小时，珠周围、动脉壁以及水肿的动脉周围和细支气管周围结缔组织就有明显的嗜酸性粒细胞和巨噬细胞浸润。动脉周围-细支气管周围嗜酸性粒细胞聚集密度在24和48小时达到峰值。在24至96小时，巨噬细胞和多核细胞在部分降解的葡聚糖珠周围的动脉炎症细胞反应中占主导。直到96小时才检测到骨髓嗜酸性粒细胞生成和血液嗜酸性粒细胞增多。我们得出结论，葡聚糖在血液嗜酸性粒细胞增多之前诱导肺部嗜酸性粒细胞增多，并表明葡聚糖可能诱导肺部释放一种或多种嗜酸性粒细胞趋化物质。该模型可能对研究影响嗜酸性粒细胞在各种疾病状态下迁移到肺部的因素有用。
