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1.
Int J Mol Sci ; 23(3)2022 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-35163636

RESUMO

Mast cells (MCs) have relevant participation in inflammatory and vascular hyperpermeability events, responsible for the action of the kallikrein-kinin system (KKS), that affect patients inflicted by the severe form of COVID-19. Given a higher number of activated MCs present in COVID-19 patients and their association with vascular hyperpermeability events, we investigated the factors that lead to the activation and degranulation of these cells and their harmful effects on the alveolar septum environment provided by the action of its mediators. Therefore, the pyroptotic processes throughout caspase-1 (CASP-1) and alarmin interleukin-33 (IL-33) secretion were investigated, along with the immunoexpression of angiotensin-converting enzyme 2 (ACE2), bradykinin receptor B1 (B1R) and bradykinin receptor B2 (B2R) on post-mortem lung samples from 24 patients affected by COVID-19. The results were compared to 10 patients affected by H1N1pdm09 and 11 control patients. As a result of the inflammatory processes induced by SARS-CoV-2, the activation by immunoglobulin E (IgE) and degranulation of tryptase, as well as Toluidine Blue metachromatic (TB)-stained MCs of the interstitial and perivascular regions of the same groups were also counted. An increased immunoexpression of the tissue biomarkers CASP-1, IL-33, ACE2, B1R and B2R was observed in the alveolar septum of the COVID-19 patients, associated with a higher density of IgE+ MCs, tryptase+ MCs and TB-stained MCs, in addition to the presence of intra-alveolar edema. These findings suggest the direct correlation of MCs with vascular hyperpermeability, edema and diffuse alveolar damage (DAD) events that affect patients with a severe form of this disease. The role of KKS activation in events involving the exacerbated increase in vascular permeability and its direct link with the conditions that precede intra-alveolar edema, and the consequent DAD, is evidenced. Therapy with drugs that inhibit the activation/degranulation of MCs can prevent the worsening of the prognosis and provide a better outcome for the patient.


Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/patologia , Permeabilidade Capilar , Sistema Calicreína-Cinina/fisiologia , Pulmão/patologia , Mastócitos/imunologia , SARS-CoV-2/imunologia , Adulto , Idoso , Autopsia , COVID-19/imunologia , COVID-19/virologia , Caspase 1/metabolismo , Feminino , Humanos , Interleucina-33/metabolismo , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/virologia , Masculino , Mastócitos/metabolismo , Mastócitos/virologia , Pessoa de Meia-Idade , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/patogenicidade
2.
Cytokine ; 131: 155118, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32403004

RESUMO

Bronchopulmonary dysplasia (BPD) is an abnormality that occurs in premature neonate lung development. The pathophysiology is uncertain, but the inflammatory response to lung injury may be the responsible pathway. The objective of this study is to evaluate the role of interleukins 6, 8, 10, and 17 through the anatomopathological and immunohistochemical study of the lungs of premature neonates with BPD. Thirty-two cases of neonatal autopsies from the Pathology Department of the Clinics Hospital of the Universidade Federal do Paraná, who presented between 1991 and 2005 were selected. The sample included neonates less than 34 weeks of gestational age who underwent oxygen therapy and had pulmonary formalin-fixed paraffin-embedded (FFPE) samples. Pulmonary specimens were later classified into three groups according to histopathological and morphometric changes (classic BPD, new BPD, and without BPD) and subjected to immunohistochemical analysis. The antibodies selected for the study were anti-IL-6, anti-IL-8, anti-IL-10, and anti-IL-17A monoclonal antibodies. IL-6, IL-8, and IL-10 showed no significant differences in tissue expression among the groups. IL-17A had higher tissue immunoreactivity in the group without BPD compared with the classic BPD group (1686 vs. 866 µm2, p = 0.029). This study showed that the involvement of interleukins 6, 8, and 10 might not be significantly different between the two types of BPD. We speculated that IL-17A could be a protective factor in this disease.


Assuntos
Displasia Broncopulmonar/imunologia , Interleucina-17/metabolismo , Interleucinas/metabolismo , Pulmão/imunologia , Displasia Broncopulmonar/patologia , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Masculino
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