Leiferman K M, Fujisawa T, Gray B H, Gleich G J
Department of Dermatology, Mayo Clinic, Rochester, Minnesota.
Lab Invest. 1990 May;62(5):579-89.
Intradermal injection of allergens in sensitive subjects produces an IgE-dependent prolonged inflammatory reaction, the late phase reaction (LPR). Histologically, eosinophils are present in the LPR but are not as numerous as neutrophils or mononuclear cells. We determined whether extracellular deposition of eosinophil and neutrophil granule proteins occurs in the LPR by immunofluorescent localization of eosinophil granule major basic protein (MBP), eosinophil-derived neurotoxin (EDN), and neutrophil elastase. Before intradermal challenge, eosinophils and neutrophils were present only in blood vessels, and MBP, EDN, and elastase were localized to cells. At 15 minutes, small amounts of MBP, EDN and elastase were found outside of cells in focal areas. By 1 to 3 hours, MBP, EDN and elastase were extensively deposited throughout the dermis in a granular and diffuse manner; these deposits persisted up to 56 hours. Both actively and passively sensitized subjects showed similar MBP and elastase deposition. Skin sites passively sensitized by sera depleted of IgE showed essentially no MBP or elastase deposition. Electron microscopy showed degenerating eosinophils and free eosinophil granules in the dermis. Mast cell numbers diminished during the LPR when extracellular eosinophil and neutrophil granule protein deposition was maximal. These results demonstrate that striking dermal eosinophil and neutrophil granule protein deposits are prominent features of the cutaneous LPR, are IgE-dependent and precede the maximal clinical expression of the LPR. The possible significance of these findings in the pathophysiology of the LPR is discussed.
在敏感个体中，皮内注射变应原会引发一种依赖IgE的持续性炎症反应，即迟发相反应（LPR）。从组织学上看，嗜酸性粒细胞存在于迟发相反应中，但数量不如中性粒细胞或单核细胞多。我们通过对嗜酸性粒细胞颗粒主要碱性蛋白（MBP）、嗜酸性粒细胞衍生神经毒素（EDN）和中性粒细胞弹性蛋白酶进行免疫荧光定位，来确定嗜酸性粒细胞和中性粒细胞颗粒蛋白在迟发相反应中是否会发生细胞外沉积。在皮内激发前，嗜酸性粒细胞和中性粒细胞仅存在于血管中，MBP、EDN和弹性蛋白酶定位于细胞内。15分钟时，在局部区域的细胞外发现少量MBP、EDN和弹性蛋白酶。到1至3小时，MBP、EDN和弹性蛋白酶以颗粒状和弥漫性的方式广泛沉积于整个真皮层；这些沉积物可持续长达56小时。主动和被动致敏的个体均显示出相似的MBP和弹性蛋白酶沉积。用去除IgE的血清进行被动致敏的皮肤部位基本未显示出MBP或弹性蛋白酶沉积。电子显微镜显示真皮中有嗜酸性粒细胞退变和游离的嗜酸性粒细胞颗粒。在迟发相反应中，当细胞外嗜酸性粒细胞和中性粒细胞颗粒蛋白沉积达到最大时，肥大细胞数量减少。这些结果表明，显著的真皮嗜酸性粒细胞和中性粒细胞颗粒蛋白沉积是皮肤迟发相反应的突出特征，依赖于IgE，并先于迟发相反应的最大临床表现出现。本文讨论了这些发现在迟发相反应病理生理学中的可能意义。
