Kawabori S, Soda K, Perdue M H, Bienenstock J
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
Lab Invest. 1991 Feb;64(2):224-33.
We examined the effects of corticosteroid treatment on eosinophils in the jejunal mucosa of rats previously infected with Nippostrongylus brasiliensis. Rats received a single intraperitoneal injection of 1 mg of dexamethasone. At a light microscopic level, the number of eosinophils with typical nuclei and granules was significantly decreased as early as 3 hours after injection, and had diminished to 17% of starting values at 24 hours. Pyknotic cells containing eosinophilic granules or fragments were observed scattered in the subepithelial interstitial space 3 and 7 hours after injection. By electron microscopy, more than 20% of eosinophils demonstrated nuclear abnormalities. Degenerating eosinophils without granular changes (27 of 127, 14.1%) or with or with granular changes (9 of 127, 7.1%) increased at 3 hours compared with untreated rats (8 of 233, 3.4%; 4 of 233, 1.7%). At 7 hours, 47 of 96 (49.0%) eosinophils were located inside phagocytic vacuoles of macrophages. Single macrophages occasionally engulfed two or more eosinophils. Only a few degeneration eosinophils (7 of 96) were observed outside macrophages. At 13 hours, the percentage of degenerating eosinophils and eosinophils inside macrophages was decreased; at 24 hours, few eosinophils were seen and eosinophil structures could not be identified inside macrophages. The epithelium and lamina propria did not show structural damage typical of an inflammatory reaction at any time. Eosinophil numbers in mesenteric lymph nodes, spleens, and peripheral blood were also reduced by dexamethasone. Similar observations were made in the jejunal mucosa of noninfected rats. We observed the slow restoration of eosinophil numbers in the intestinal wall, finally reaching preinjection numbers after 14 days. We conclude that dexamethasone has important effects on eosinophils causing (a) nuclear degeneration and (b) changes in the granular matrix. Subsequently, these damaged eosinophils are engulfed by macrophages and swiftly disappear from the intestinal mucosa. These effects appear to be due to the induction of apoptosis. Our findings offer an explanation for one of the significant antiinflammatory effects observed with the use of corticosteroids.
我们研究了皮质类固醇治疗对先前感染巴西日圆线虫的大鼠空肠黏膜中嗜酸性粒细胞的影响。大鼠腹腔注射1毫克地塞米松。在光学显微镜下，早在注射后3小时，具有典型细胞核和颗粒的嗜酸性粒细胞数量就显著减少，在24小时时已降至初始值的17%。在注射后3小时和7小时，观察到含有嗜酸性颗粒或碎片的固缩细胞散在于上皮下间隙。通过电子显微镜观察，超过20%的嗜酸性粒细胞表现出核异常。与未治疗的大鼠相比，在3小时时，无颗粒变化的退化嗜酸性粒细胞（127个中的27个，14.1%）或有颗粒变化的退化嗜酸性粒细胞（127个中的9个，7.1%）数量增加（233个中的8个，3.4%；233个中的4个，1.7%）。在7小时时，96个嗜酸性粒细胞中有47个（49.0%）位于巨噬细胞的吞噬泡内。单个巨噬细胞偶尔会吞噬两个或更多嗜酸性粒细胞。在巨噬细胞外仅观察到少数退化嗜酸性粒细胞（96个中的7个）。在13小时时，退化嗜酸性粒细胞和巨噬细胞内嗜酸性粒细胞的百分比下降；在24小时时，几乎看不到嗜酸性粒细胞，在巨噬细胞内也无法识别嗜酸性粒细胞结构。上皮和固有层在任何时候都未显示出典型炎症反应的结构损伤。地塞米松还可减少肠系膜淋巴结、脾脏和外周血中的嗜酸性粒细胞数量。在未感染大鼠的空肠黏膜中也观察到了类似现象。我们观察到肠壁中嗜酸性粒细胞数量缓慢恢复，最终在14天后达到注射前数量。我们得出结论，地塞米松对嗜酸性粒细胞有重要影响，导致（a）核变性和（b）颗粒基质变化。随后，这些受损的嗜酸性粒细胞被巨噬细胞吞噬，并迅速从肠黏膜中消失。这些作用似乎是由于诱导细胞凋亡所致。我们的研究结果为使用皮质类固醇所观察到的显著抗炎作用之一提供了解释。
