HIV gp120 Induces the Release of Proinflammatory, Angiogenic, and Lymphangiogenic Factors from Human Lung Mast Cells.

Giancarlo Marone,Antonio Pecoraro,Giuseppe Spadaro,Francesca Wanda Rossi,Amato De Paulis,Gilda Varricchi,Gjada Criscuolo,Gianni Marone,Valentina Pucino

doi:10.3390/vaccines8020208

Abstract

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 (VH3) 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 C4 (LTC4) and prostaglandin D2 (PGD2) 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 VH3+ 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.

Highlights

The human immunodeficiency virus (HIV-1) affects more than 36 million people worldwide [Unaids
In this study we evaluated whether viral gp120 superantigen can induce the release of proinflammatory, angiogenic, and lymphangiogenic factors from primary mast cells isolated from human lung parenchyma
The activating property of Hhistamine secretion four different of Human lung mast cells (HLMCs) isolated from subjects aIgE is from mediated by the interactionpreparations with immunoglobulin E (IgE) on basophils and mast cells

Summary

Introduction

The human immunodeficiency virus (HIV-1) affects more than 36 million people worldwide [Unaids. The combined antiretroviral therapy (ART) can successfully suppress HIV viremia and delays the progression of disease [1], the chronic infection. A significant percentage of HIV-infected individuals has hepatitis C virus (HCV) co-infection [5] resulting in increased. HIV reservoir size [6]. The advent of ART has improved survival of HIV-infected adults and children leading to chronic illnesses such as different pulmonary diseases [7,8]. Chronic obstructive pulmonary disease (COPD), asthma, pulmonary hypertension, lung cancer, and asthma are prevalent among HIV patients [7,9,10,11,12,13]

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