Patella V, de Crescenzo G, Marinò I, Genovese A, Adt M, Gleich G J, Marone G
Division of Clinical Immunology, University of Naples Federico II, School of Medicine, Naples, Italy.
J Immunol. 1996 Aug 1;157(3):1219-25.
Eosinophilia in humans is often associated with heart disease and cardiac localization of eosinophil granule proteins, and several results suggest that granule proteins mediate endomyocardial damage. Here we investigated the in vitro effects of the four principal eosinophil granule proteins (eosinophil cationic protein (ECP), major basic protein (MBP), eosinophil-derived neurotoxin, and eosinophil peroxidase (EPO)) on the activation of effector cells of inflammation (mast cells) isolated from human heart tissue (HHMC). ECP and, to a lesser extent, MBP (0.3-3 microM), but not eosinophil-derived neurotoxin and eosinophil peroxidase stimulated the release of preformed (histamine and tryptase) and the de novo synthesis of vasoactive and proinflammatory mediators (PGD2) from HHMC. Activation of HHMC by ECP and MBP was Ca2+- and temperature-dependent and was abolished by preincubation (15 min, 37 degrees C) with 2-deoxy-D-glucose (10 mM) and antimycin A (1 microM). There was a significant correlation between the maximal percentage of histamine release induced by ECP and anti-IgE from HHMC (rs = 0.73; p < 0.005), by MBP and anti-IgE (rs = 0.79; p < 0.001), and by ECP and MBP (rs = 0.65; p < 0.005). A positive correlation was also found between histamine and tryptase secretion (rs = 0.71; p < 0.001) and between histamine and PGD2 release induced by ECP from HHMC (rs = 0.85; p < 0.001). This is the first demonstration that some eosinophil cationic proteins, namely ECP and MBP, found at the site of heart damage in patients with eosinophilia, act as complete secretagogues on HHMC. This observation indicates another mechanism by which infiltrating eosinophils and their metabolic products cause inflammatory reactions and thus endomyocardial lesions in patients with eosinophilia.
人类嗜酸性粒细胞增多常与心脏病以及嗜酸性粒细胞颗粒蛋白在心脏的定位有关，多项研究结果表明颗粒蛋白介导心内膜损伤。在此，我们研究了四种主要的嗜酸性粒细胞颗粒蛋白（嗜酸性粒细胞阳离子蛋白（ECP）、主要碱性蛋白（MBP）、嗜酸性粒细胞衍生神经毒素和嗜酸性粒细胞过氧化物酶（EPO））对从人心脏组织分离的炎症效应细胞（肥大细胞，即HHMC）激活的体外影响。ECP以及程度稍轻的MBP（0.3 - 3 microM）可刺激HHMC释放预先形成的物质（组胺和类胰蛋白酶）以及血管活性和促炎介质（PGD2）的从头合成，但嗜酸性粒细胞衍生神经毒素和嗜酸性粒细胞过氧化物酶则无此作用。ECP和MBP对HHMC的激活呈Ca2 +和温度依赖性，并可通过与2 - 脱氧 - D - 葡萄糖（10 mM）和抗霉素A（1 microM）预孵育（15分钟，37摄氏度）而被消除。ECP和抗IgE诱导HHMC释放组胺的最大百分比之间（rs = 0.73；p < 0.005）、MBP和抗IgE之间（rs = 0.79；p < 0.001）以及ECP和MBP之间（rs = 0.65；p < 0.005）存在显著相关性。组胺和类胰蛋白酶分泌之间（rs = 0.71；p < 0.001）以及ECP诱导HHMC释放组胺和PGD2之间（rs = 0.85；p < 0.001）也发现呈正相关。这是首次证明在嗜酸性粒细胞增多患者心脏损伤部位发现的某些嗜酸性粒细胞阳离子蛋白，即ECP和MBP，对HHMC具有完全的促分泌作用。该观察结果表明了另一种机制，即浸润的嗜酸性粒细胞及其代谢产物在嗜酸性粒细胞增多患者中引起炎症反应并进而导致心内膜病变。
