Giant Multinucleated Cells Are Associated with Mastocytic Inflammatory Signature Equine Asthma (original) (raw)
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AJP: Lung Cellular and Molecular Physiology, 2012
Heaves, an obstructive neutrophilic airway inflammation of horses, is triggered by dust components such as endotoxin and has similarities to human asthma. Pulmonary intravascular macrophages (PIMs) increase horses' sensitivity to endotoxin-induced lung inflammation; however, their role in an airborne pathology remains unknown. Therefore, we investigated the role of PIMs in the development of heaves in horses. Clinical and inflammatory responses were evaluated following induction of heaves by moldy hay exposure and PIM depletion with gadolinium chloride (GC). Mares ( N = 9) were exposed to four treatments: alfalfa cubes (Cb), alfalfa cubes + GC (Cb-GC), moldy hay (MH), and moldy hay + GC (MH-GC). Clinical scores and neutrophil concentrations in bronchoalveolar lavage (BAL) fluid were higher when mares received MH compared with MH-GC. BAL cells from MH-GC-treated mares had significantly lower IL-8 and TLR4 mRNA expression compared with MH-treated mares. In vitro LPS challenge sign...
Frontiers in Immunology
Equine asthma (EA) is a highly relevant disease, estimated to affect up to 20% of all horses, and compares to human asthma. The pathogenesis of EA is most likely immune-mediated, yet incompletely understood. To study the immune response in the affected lower airways, mixed leukocytes were acquired through bronchoalveolar lavage (BAL) and the cell populations were analyzed on a single-cell basis by flow cytometry (FC). Samples of 38 horses grouped as respiratory healthy or affected by mild to moderate (mEA) or severe EA (sEA) according to their history, clinical signs, and BAL cytology were analyzed. Using FC, BAL cells and PBMC were comprehensively characterized by cell surface markers ex vivo. An increased percentage of DH24A+ polymorphonuclear cells, and decreased percentages of CD14+ macrophages were detected in BAL from horses with sEA compared to healthy horses or horses with mEA, while lymphocyte proportions were similar between all groups. Independently of EA, macrophages in ...
Pulmonary Remodeling in Equine Asthma: What Do We Know about Mediators of Inflammation in the Horse?
Mediators of Inflammation
Equine inflammatory airway disease (IAD) and recurrent airway obstruction (RAO) represent a spectrum of chronic inflammatory disease of the airways in horses resembling human asthma in many aspects. Therefore, both are now described as severity grades of equine asthma. Increasing evidence in horses and humans suggests that local pulmonary inflammation is influenced by systemic inflammatory processes and the other way around. Inflammation, coagulation, and fibrinolysis as well as extracellular remodeling show close interactions. Cytology of bronchoalveolar lavage fluid and tracheal wash is commonly used to evaluate the severity of local inflammation in the lung. Other mediators of inflammation, like interleukins involved in the chemotaxis of neutrophils, have been studied. Chronic obstructive pneumopathies lead to remodeling of bronchial walls and lung parenchyma, ultimately causing fibrosis. Matrix metalloproteinases (MMPs) are discussed as the most important proteolytic enzymes dur...
Increased leishmanicidal activity of alveolar macrophages from mature horses with mild equine asthma
Arquivo Brasileiro de Medicina Veterinária e Zootecnia, 2019
Alveolar macrophages (AMs) are an essential part of defense mechanisms within the lungs and their phagocytic activity is important for organ homeostasis. The phagocytic ability of AMs obtained from bronchoalveolar lavage from 17 mature mixed-breed pleasure horses (8 healthy and 9 diagnosed with mild equine asthma) was studied through assays with Leishmania (Viannia) braziliensis promastigotes, which enabled the calculation of a phagocytic index (PI) and a survival index (SI). Results indicate that phagocytic activity of AMs in asthma affected horses is similar to healthy horses, while leishmanicidal activity is significantly increased in horses with asthma.
The Immune Mechanisms of Severe Equine Asthma—Current Understanding and What Is Missing
Animals, 2022
Severe equine asthma is a chronic respiratory disease of adult horses, occurring when genetically susceptible individuals are exposed to environmental aeroallergens. This results in airway inflammation, mucus accumulation and bronchial constriction. Although several studies aimed at evaluating the genetic and immune pathways associated with the disease, the results reported are inconsistent. Furthermore, the complexity and heterogeneity of this disease bears great similarity to what is described for human asthma. Currently available studies identified two chromosome regions (ECA13 and ECA15) and several genes associated with the disease. The inflammatory response appears to be mediated by T helper cells (Th1, Th2, Th17) and neutrophilic inflammation significantly contributes to the persistence of airway inflammatory status. This review evaluates the reported findings pertaining to the genetical and immunological background of severe equine asthma and reflects on their implications i...
European Respiratory Journal, 1994
A Al lv ve eo ol la ar r m ma ac cr ro op ph ha ag ge e--i in nd du uc ce ed d s su up pp pr re es ss si io on n o of f p pe er ri ip ph he er ra al l b bl lo oo od d m mo on no on nu uc cl le ea ar r c ce el ll l r re es sp po on ns si iv ve en ne es ss s i is s r re ev ve er rs se ed d b by y i in n v vi it tr ro o a al ll le er rg ge en n e ex xp po os su ur re e i in n b br ro on nc ch hi ia al l a as st th hm ma a Alveolar macrophage-induced suppression of peripheral blood mononuclear cell responsiveness is reversed by in vitro allergen exposure in bronchial asthma. ABSTRACT: Little information is available on the specific role of alveolar macrophages (AMs) in modulating local cellular reactions to inhaled allergens in atopic asthma.
Immunophenotypic characterization and depletion of pulmonary intravascular macrophages of horses
Veterinary Research, 2004
Pulmonary intravascular macrophages (PIMs) are present in horses and are believed to increase their sensitivity to endotoxin-induced cardio-pulmonary shock. However, owing to a lack of a marker for PIMs and the inability to isolate them, their precise contributions in the horse remain unknown. We designed this study to identify an immuno-phenotypic marker for PIMs and to develop a protocol for their transient depletion with gadolinium chloride (GC). GC is a lanthanide that has been used to deplete liver and lung macrophages. The horses (N = 15) were divided into control (n = 5) and GC-treated (n = 10) groups and the lung samples were examined by routine and immunocytochemical light and electron microscopy. GC-treated horses were euthanized at 48 h (n = 6) and 72 h (n = 4) post-treatment. The PIMs reacted with MAC-387 but not with ED-1 and CD-68 anti-macrophage antibodies. GC reduced the number of PIMs in horses at 48 and 72 h compared with the control (p < 0.05). There were increased intravascular TUNEL-positive cells in GC-treated horses and electron microscopy showed apoptotic PIMs in these horses. These data show that MAC-387 is a reliable marker for PIMs and GC is a safe tool to reduce the number of PIMs. PIMs / gadolinium / MAC-387 / apoptosis / immunohistology / immuno-electron microscopy / TUNEL
Faculty of 1000 evaluation for Alternative macrophage activation is increased in asthma
F1000 - Post-publication peer review of the biomedical literature, 2017
The immune responses of type 2 T helper cells (Th2) play an important role in asthma and promote the differentiation of alternatively activated (M2) macrophages. M2 macrophages have been increasingly understood to contribute to Th2 immunity. We hypothesized that M2 macrophages are altered in asthma and modulate Th2 responses. The aim of this study was to characterize the phenotype and function of human monocyte-derived M2 and bronchoalveolar lavage fluid (BALF) macrophages from healthy control subjects and subjects with asthma. Phenotypic characteristics and effector function of M2 macrophages were examined using monocyte-derived and BALF macrophages obtained from subjects with asthma (n = 28) and healthy volunteers (n = 9) by flow cytometry and quantitative PCR. Resting monocyte-derived (M0) and M2 macrophages were generated by the addition of macrophage colony-stimulating factor or macrophage colony-stimulating factor plus IL-4, respectively. M2 macrophage cytokine expression and their impact on dendritic and CD4 1 T cell activation were examined in vitro. High levels of CD206 and major histocompatibility complex class II expression identify macrophages with an M2 phenotype that are increased 2.9-fold in the BALF of subjects with asthma compared with control subjects. M2 macrophages have elevated IL-6, IL-10, and IL-12p40 production compared with conventional macrophages and modulate dendritic and CD4 1 T cell interactions. Histamine receptor 1 and E-cadherin expression identify M2 macrophage subsets associated with increased airflow obstruction. M2 macrophages have a distinct cell surface and effector phenotype and are found in increased numbers in subjects with asthma. These findings suggest that M2 macrophages may play an important role in allergic asthma through their bidirectional interactions with immune and structural cells, and inflammatory mediators.