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1.
Pathologie (Heidelb) ; 45(4): 261-268, 2024 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-38805092

RESUMO

BACKGROUND: Diseases of the nonneoplastic renal parenchyma occur in the context of a number of disorders that affect the organism systemically and can thus represent a differential diagnosis for autoimmunological kidney diseases. PURPOSE: Two common autoimmunologic diseases of the kidney, namely antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and systemic lupus erythematosus (SLE), are presented and put into context of the broader field of renal diseases. Novel diagnostic and therapeutic approaches are discussed. MATERIALS AND METHODS: A review of the recent literature and an overview of the disease presentation are provided.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Nefropatias , Lúpus Eritematoso Sistêmico , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/patologia , Lúpus Eritematoso Sistêmico/diagnóstico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/patologia , Nefropatias/patologia , Nefropatias/etiologia , Nefropatias/diagnóstico , Diagnóstico Diferencial , Rim/patologia
2.
Hepatol Commun ; 8(1)2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38099865

RESUMO

BACKGROUND: Posthepatectomy liver failure (PHLF) represents a life-threatening complication with limited therapeutic options. Neutrophils play a critical and dynamic role during regeneratory processes, but their role in human liver regeneration is incompletely understood, especially as underlying liver disease, detectable in the majority of patients, critically affects hepatic regeneration. Here we explored intrahepatic neutrophil accumulation and neutrophil extracellular traps (NETs) in patients with PHLF and validated the functional relevance of NETs in a murine partial hepatectomy (PHx) model. METHODS: We investigated the influx of neutrophils, macrophages, eosinophils, and mast cells and the presence of their respective extracellular traps in liver biopsies of 35 patients undergoing hepatectomy (10 patients with PHLF) before and after the initiation of liver regeneration by fluorescence microscopy. In addition, NET formation and neutrophil activation were confirmed by plasma analysis of 99 patients (24 patients with PHLF) before and up to 5 days after surgery. Furthermore, we inhibited NETs via DNase I in a murine PHx model of mice with metabolically induced liver disease. RESULTS: We detected rapid intrahepatic neutrophil accumulation, elevated levels of myeloperoxidase release, and NET formation in regenerating human livers, with a significantly higher increase of infiltrating neutrophils and NETs in patients with PHLF. Circulating markers of neutrophil activation, including elastase, myeloperoxidase, and citrullinated histone H3, correlated with markers of liver injury. In a murine PHx model, we showed that the inhibition of NET accelerated hepatocyte proliferation and liver regeneration. CONCLUSIONS: Patients with PHLF showed accelerated intrahepatic neutrophil infiltration and NET formation, which were associated with liver damage. Further, we identified postsurgical myeloperoxidase levels as predictive markers for adverse outcomes and observed that blocking NETs in a murine PHx model accelerated tissue regeneration.


Assuntos
Armadilhas Extracelulares , Hiperplasia Nodular Focal do Fígado , Falência Hepática , Humanos , Animais , Camundongos , Neutrófilos , Falência Hepática/etiologia , Peroxidase
3.
J Extracell Biol ; 2(5): e88, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-38938276

RESUMO

Small extracellular vesicles (sEV) purified from blood have great potential clinically as biomarkers for systemic disease; however interpretation is complicated by release of sEV ex vivo after blood taking. To quantify the problem and devise ways to minimise it, we characterised sEV in paired serum, plasma and platelet poor plasma (PPP) samples from healthy donors. Immunoblotting showed twofold greater abundance of CD9 in sEV fractions from fresh serum than from fresh plasma or PPP. MACSPlex confirmed this, and showed that proteins expressed on platelet sEV, either exclusively (CD41b, CD42a and CD62P) or more widely (HLA-ABC, CD24, CD29 and CD31) were also twofold more abundant; by contrast non-platelet proteins (including CD81) were no different. Storage of plasma (but not serum) increased abundance of platelet and selected leukocyte sEV proteins to at least that of serum, and this could be recapitulated by activating cells in fresh plasma by Ca2+, an effect abrogated in PPP. This suggests that a substantial proportion of sEV in serum and stored plasma were generated ex vivo, which is not the case for fresh plasma or PPP. Thus we provide strategies to minimise ex vivo sEV generation and criteria for identifying those that were present in vivo.

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