scholarly journals Mast cells are associated with exacerbations and eosinophilia in children with severe asthma

2016 ◽  
Vol 48 (5) ◽  
pp. 1320-1328 ◽  
Author(s):  
Guillaume Lezmi ◽  
Louise Galmiche-Rolland ◽  
Sabine Rioux ◽  
Francis Jaubert ◽  
Isabelle Tillie-Leblond ◽  
...  

The role of mast cells in the pathogenesis of childhood asthma is poorly understood. We aimed to estimate the implication of airway mucosal mast cells in severe asthma and their relationship with clinical, functional, inflammatory and remodelling parameters.Bronchial biopsies were performed in 36 children (5–18 years) with severe asthma: 24 had frequent severe exacerbations and/or daily symptoms in the previous year (symptomatic group), and 12 had few symptoms and a persistent obstructive pattern (paucisymptomatic group). Nine children without asthma were included as control subjects. We assessed mast cells in the submucosa and airway smooth muscle using c-kit antibodies and in the entire biopsy area using Giemsa.The number of submucosal mast cells was higher in the symptomatic group than in the paucisymptomatic group (p=0.02). The number of submucosal mast cells correlated with the number of severe exacerbations (p=0.02, r=0.37). There were positive correlations between the number of submucosal mast cells (p<0.01, r=0.44), airway smooth muscle mast cells (p=0.02, r= 0.40), mast cells stained by Giemsa (p<0.01, r=0.44) and submucosal eosinophils.Mast cells are associated with severe exacerbations and submucosal eosinophilic inflammation in children with severe asthma.

2018 ◽  
Vol 194 (2) ◽  
pp. 253-258 ◽  
Author(s):  
L. Chachi ◽  
A. Alzahrani ◽  
C. Koziol-White ◽  
M. Biddle ◽  
R. Bagadood ◽  
...  

2021 ◽  
Author(s):  
Rebeca Fraga-Iriso ◽  
Óscar Amor-Carro ◽  
Nadia S. Brienza ◽  
Laura Núñez-Naveira ◽  
Beatriz Lema-Costa ◽  
...  

AbstractRationaleInvestigations on the mechanisms of airway smooth muscle remodeling, a prominent asthma feature contributing to its clinical manifestations and severity, have largely focused on its hyperplastic growth. Conversely, limited data and virtually no translational research have been produced on a plausible role of apoptosis in the homeostasis and remodeling of airway smooth muscle.ObjectivesWe aimed at demonstrating an involvement of apoptosis, an essential regulator of organ structure and cell turnover, in the pathophysiology of airway smooth muscle remodeling in asthma.MethodsMurine experimental asthma was modeled to analyze airway hyperresponsiveness, contractile tissue remodeling and apoptosis detection outcomes at early and late cutoffs, and under pharmacological inhibition of apoptosis by employing a caspase blocker. Clinical investigation followed through analyses on human bronchial biopsies.ResultsAirway hyperresponsiveness and contractile tissue remodeling were already established in early experimental asthma, and a subsequent upregulation of apoptosis limited the airway contractile tissue growth. Caspase inhibition elicited chaotic pulmonary mechanics and an unusual growth of airway smooth muscle that was structurally disorganized. In bronchial biopsies, airway smooth muscle increased from controls through subjects with intermittent and persistent moderate and severe asthma. Cleaved poly-ADP ribose polymerase (c-PARP, a byproduct of caspase activity) was increased in severe asthma.ConclusionsApoptosis is involved in airway contractile cell turnover and in shaping the size, structure and proper function of the airway smooth muscle layer. Apoptosis inhibitors may complicate concomitant asthma, whereas agents favouring airway contractile cell apoptosis may provide a novel pipeline of therapeutic development.Key messagesHow normal airway smooth muscle structure is preserved, and whether counteracting responses to remodeling are elicited in asthma, are outstanding questions not probed in vivo nor in the clinical setting.In this work, combined investigations on murine experimental asthma and human bronchial biopsies show that airway contractile cell apoptosis is involved in the homeostasis of airway smooth muscle, and apoptotic activity is upregulated as part of the remodeling process of this tissue in asthma.Apoptosis arises as a key regulator of the size and structure of the airway smooth muscle layer. This concept draws implications for clinical practice and drug development.


Author(s):  
Latifa Chachi ◽  
Mahnaz Abbasian ◽  
Adelina Gavrila ◽  
Omar Tliba ◽  
Christopher Brightling ◽  
...  

Author(s):  
Jameel Hakeem ◽  
Latifa Chachi ◽  
Fahad Alhadian ◽  
Michael Biddle ◽  
Omar Tliba ◽  
...  

Author(s):  
Tomoko Yamaguchi ◽  
Yumi Ikeda ◽  
Katsuhisa Tashiro ◽  
Yasuyuki Ohkawa ◽  
Kenji Kawabata

2013 ◽  
Vol 65 ◽  
pp. S104
Author(s):  
Manuel Alejandro Ramirez-Lee ◽  
Hector Rosas-Hernandez ◽  
Samuel Salazar-Garcia ◽  
Jose Manuel Gutiérrez-Hernández ◽  
Ricardo Espinosa- Tanguma ◽  
...  

2015 ◽  
Vol 90 (6) ◽  
pp. 2928-2937 ◽  
Author(s):  
Ai-Ping Jiang ◽  
Jin-Feng Jiang ◽  
Ji-Fu Wei ◽  
Ming-Gao Guo ◽  
Yan Qin ◽  
...  

ABSTRACTThe gastrointestinal mucosa is the primary site where human immunodeficiency virus type 1 (HIV-1) invades, amplifies, and becomes persistently established, and cell-to-cell transmission of HIV-1 plays a pivotal role in mucosal viral dissemination. Mast cells are widely distributed in the gastrointestinal tract and are early targets for invasive pathogens, and they have been shown to have increased density in the genital mucosa in HIV-infected women. Intestinal mast cells express numerous pathogen-associated molecular patterns (PAMPs) and have been shown to combat various viral, parasitic, and bacterial infections. However, the role of mast cells in HIV-1 infection is poorly defined. In this study, we investigated their potential contributions to HIV-1 transmission. Mast cells isolated from gut mucosal tissues were found to express a variety of HIV-1 attachment factors (HAFs), such as DC-SIGN, heparan sulfate proteoglycan (HSPG), and α4β7 integrin, which mediate capture of HIV-1 on the cell surface. Intriguingly, following coculture with CD4+T cells, mast cell surface-bound viruses were efficiently transferred to target T cells. Prior blocking with anti-HAF antibody or mannan before coculture impaired viraltrans-infection. Cell-cell conjunctions formed between mast cells and T cells, to which viral particles were recruited, and these were required for efficient cell-to-cell HIV-1 transmission. Our results reveal a potential function of gut mucosal mast cells in HIV-1 dissemination in tissues. Strategies aimed at preventing viral capture and transfer mediated by mast cells could be beneficial in combating primary HIV-1 infection.IMPORTANCEIn this study, we demonstrate the role of human mast cells isolated from mucosal tissues in mediating HIV-1trans-infection of CD4+T cells. This finding facilitates our understanding of HIV-1 mucosal infection and will benefit the development of strategies to combat primary HIV-1 dissemination.


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