Secreted Phospholipases A2 in Hereditary Angioedema With C1-Inhibitor Deficiency

Loffredo, Stefania; Ferrara, Anne Lise; Bova, María; Borriello, Francesco; Suffritti, Chiara; Veszeli, Nóra; Petraroli, Angelica; Galdiero, Maria Rosaria; Varricchi, Gilda; Granata, Francescopaolo; Zanichelli, Andrea; Farkas, Henriette; Cicardi, Marco; Lambeau, Gérard; Marone, Gianni

doi:10.3389/fimmu.2018.01721

Cited by 23 publications

(33 citation statements)

References 67 publications

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“…At the end of incubation, cells were centrifuged (1000× g , 4 °C, 5 min) and the supernatants were stored at −80 °C for subsequent assay of mediator release. VEGF-A and VEGF-C were measured in duplicate determinations using ELISA kits (R&D System, Minneapolis, MN, USA [ 90 ]. The ELISA sensitivity is 31.1–2000 pg/mL for VEGF-A and 62–4000 pg/mL for VEGF-C.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2020

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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.

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Section: Methodsmentioning

confidence: 99%

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

et al. 2020

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“…J Investig Allergol Clin Immunol 2021; Vol. 31 (5) © 2020 Esmon Publicidad doi: 10.18176/jiaci.0524 NVC NVC (VideoCap® 3.0-D1, DS Medica, Milan, Italy) is a highly sensitive, inexpensive, simple, safe, and noninvasive imaging technique used in the morphological analysis of nourishing capillaries in the nailfold area [8].…”

Section: Introductionmentioning

confidence: 99%

Nailfold Videocapillaroscopy Findings in Bradykinin-Mediated Angioedema

Marcelli

Loffredo

Petraroli

et al. 2021

J Investig Allergol Clin Immunol

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Background: Hereditary angioedema with C1-inhibitor deficiency (C1-INH-HAE) and acquired angioedema related to ACE inhibitors (ACEI-AAE) are types of bradykinin-mediated angioedema without wheals characterized by recurrent swelling episodes. Recent evidence suggests that a state of "vascular preconditioning" predisposes individuals to attacks, but no data are available on the possible structural alterations of the vessels. Objective: This study aims at evaluating the features of the nailfold capillaries to highlight possible structural anomalies in patients affected by C1-INH-HAE in comparison with the healthy population and ACEI-AAE patients in comparison with hypertensive controls. Methods: With nailfold videocapillaroscopy (NVC), we assessed: apical, internal, and external diameter, loop length, intercapillary distance, capillary density, distribution, and morphology. Plasma levels of vascular endothelial growth factor (VEGF)-A, VEGF-C, angiopoietin (Ang)1, and Ang2 were also measured. Results: C1-INH-HAE patients (n = 34) had significant structural alterations of the capillaries compared to healthy controls (n = 28): greater intercapillary distance (216 vs 190 µm), increased apical, internal, and external diameter (28 vs 22 µm; 22 vs 20 µm; and 81 vs 65 µm, respectively), decreased density (4 vs 5 capillaries/mm 2), more irregular capillary distribution, and more tortuous morphology. Apical diameter was enlarged in patients with ≥12 attacks/year. In ACEI-AAE patients, NVC showed no alterations versus hypertensive controls. NVCs performed in two C1-INH-HAE patients during attacks showed no changes compared to the remission phase. Conclusions: C1-INH-HAE patients have important structural capillary alterations, confirming the involvement of microcirculation in the pathogenesis of angioedema.

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“…sPLA 2 modulates vascular permeability [ 55 ] and promotes inflammation [ 52 , 53 , 56 ]. Circulating sPLA 2 levels increase the risk of early atherosclerosis [ 62 ] and predict long-term mortality of HF after myocardial infarction [ 60 ].…”

Section: Resultsmentioning

confidence: 99%

“…PLA 2 activity was found increased in plasma from both groups of HF patients compared to healthy controls. PLA 2 modulates endothelial cell migration and vascular permeability in vitro and in humans [ 53 , 55 , 56 , 57 , 81 ]. Previous studies have demonstrated that circulating levels of sPLA 2 predict coronary events in patients with coronary artery disease [ 58 ], as well as in apparently healthy men and women [ 59 ].…”

Section: Discussionmentioning

confidence: 99%

“…Phospholipases A 2 (PLA 2 ) hydrolyze the fatty acids from membrane phospholipids releasing arachidonic acid and lysophospholipids [ 51 , 52 , 53 , 54 ]. Secreted or extracellular PLA 2 (sPLA 2 ) modulate vascular permeability [ 55 ] and activate inflammatory cells [ 53 , 56 , 57 ]. Circulating levels of sPLA 2 predict coronary events in patients with coronary artery disease [ 58 ] and in apparently healthy men and women [ 59 ].…”

Section: Introductionmentioning

confidence: 99%

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Angiopoietins, Vascular Endothelial Growth Factors and Secretory Phospholipase A2 in Ischemic and Non-Ischemic Heart Failure

Varricchi

Loffredo

Bencivenga

et al. 2020

JCM

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Heart failure (HF) is a growing public health burden, with high prevalence and mortality rates. In contrast to ischemic heart failure (IHF), the diagnosis of non-ischemic heart failure (NIHF) is established in the absence of coronary artery disease. Angiopoietins (ANGPTs), vascular endothelial growth factors (VEGFs) and secretory phospholipases A2 (sPLA2s) are proinflammatory mediators and key regulators of endothelial cells. In the present manuscript, we analyze the plasma concentrations of angiogenic (ANGPT1, ANGPT2, VEGF-A) and lymphangiogenic (VEGF-C, VEGF-D) factors and the plasma activity of sPLA2 in patients with IHF and NIHF compared to healthy controls. The concentrations of ANGPT1, ANGPT2 and their ratio significantly differed between HF patients and healthy controls. Similarly, plasma levels of VEGF-D and sPLA2 activity were higher in HF as compared to controls. Concentrations of ANGPT2 and the ANGPT2/ANGPT1 ratio (an index of vascular permeability) were increased in NIHF patients. VEGF-A and VEGF-C concentrations did not differ among the three examined groups. Interestingly, VEGF-D was selectively increased in IFH patients compared to controls. Plasma activity of sPLA2 was increased in IHF and NIHF patients compared to controls. Our results indicate that several regulators of vascular permeability and smoldering inflammation are specifically altered in IHF and NIHF patients. Studies involving larger cohorts of these patients will be necessary to demonstrate the clinical implications of our findings.

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Secreted Phospholipases A2 in Hereditary Angioedema With C1-Inhibitor Deficiency

Cited by 23 publications

References 67 publications

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

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

Nailfold Videocapillaroscopy Findings in Bradykinin-Mediated Angioedema

Angiopoietins, Vascular Endothelial Growth Factors and Secretory Phospholipase A2 in Ischemic and Non-Ischemic Heart Failure

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