Marone Giancarlo, Rossi Francesca Wanda, Pecoraro Antonio, Pucino Valentina, Criscuolo Gjada, Paulis Amato de, Spadaro Giuseppe, Marone Gianni, Varricchi Gilda
Department of Public Health, Section of Hygiene, University of Naples Federico II, 80138 Naples, Italy.
Azienda Ospedaliera Ospedali dei Colli, Monaldi Hospital Pharmacy, 80131 Naples, Italy.
Vaccines (Basel). 2020 May 3;8(2):208. doi: 10.3390/vaccines8020208.
Human lung mast cells (HLMCs) express the high-affinity receptor FcεRI for IgE and are involved in chronic pulmonary diseases occurring at high frequency among HIV-infected individuals. Immunoglobulin superantigens bind to the variable regions of either the heavy or light chain of immunoglobulins (Igs). Glycoprotein 120 (gp120) of HIV-1 is a typical immunoglobulin superantigen interacting with the heavy chain, variable 3 (V3) region of human Igs. The present study investigated whether immunoglobulin superantigen gp120 caused the release of different classes of proinflammatory and immunoregulatory mediators from HLMCs. The results show that gp120 from different clades induced the rapid (30 min) release of preformed mediators (histamine and tryptase) from HLMCs. gp120 also caused the de novo synthesis of cysteinyl leukotriene C (LTC) and prostaglandin D (PGD) from HLMCs. Incubation (6 h) of HLMC with gp120 induced the release of angiogenic (VEGF-A) and lymphangiogenic (VEGF-C) factors from HLMCs. The activating property of gp120 was mediated through the interaction with IgE V3 bound to FcεRI. Our data indicate that HIV gp120 is a viral superantigen, which induces the release of different proinflammatory, angiogenic, and lymphangiogenic factors from HLMCs. These observations could contribute to understanding, at least in part, the pathophysiology of chronic pulmonary diseases in HIV-infected individuals.
人肺肥大细胞（HLMCs）表达IgE的高亲和力受体FcεRI，并参与HIV感染个体中高频发生的慢性肺部疾病。免疫球蛋白超抗原与免疫球蛋白（Igs）重链或轻链的可变区结合。HIV-1的糖蛋白120（gp120）是一种典型的免疫球蛋白超抗原，与人Igs的重链可变3（V3）区相互作用。本研究调查了免疫球蛋白超抗原gp120是否会导致HLMCs释放不同类别的促炎和免疫调节介质。结果表明，来自不同进化枝的gp120诱导HLMCs快速（30分钟）释放预先形成的介质（组胺和类胰蛋白酶）。gp120还导致HLMCs从头合成半胱氨酰白三烯C（LTC）和前列腺素D（PGD）。用gp120孵育HLMCs（6小时）可诱导HLMCs释放血管生成因子（VEGF-A）和淋巴管生成因子（VEGF-C）。gp120的激活特性是通过与结合到FcεRI的IgE V3相互作用介导的。我们的数据表明，HIV gp120是一种病毒超抗原，可诱导HLMCs释放不同的促炎、血管生成和淋巴管生成因子。这些观察结果至少可以部分有助于理解HIV感染个体慢性肺部疾病的病理生理学。
