Animal models have been developed to investigate specific components of asthmatic airway inflammation, hyper-responsiveness or remodelling. However, all of these aspects are rarely observed in the same animal. Heaves is a naturally occurring disease of horses that combines these features. It is characterized by stable dust-induced inflammation, bronchospasm and remodelling. The evaluation of horses during well-controlled natural antigen exposure and avoidance in experimental settings allows the study of disease mechanisms in the asymptomatic and symptomatic stages, an approach rarely feasible in humans. Also, the disease can be followed over several years to observe the cumulative effect of repeated episodes of clinical exacerbation or to evaluate long-term treatment, contrasting most murine asthma models. This model has shown complex gene and environment interactions, the involvement of both innate and adaptive responses to inflammation, and the contribution of bronchospasm and tissue remodelling to airway obstruction, all occurring in a natural setting. Similarities with the human asthmatic airways are well described and the model is currently being used to evaluate airway remodelling and its reversibility in ways that are not possible in people for ethical reasons. Tools including antibodies, recombinant proteins or gene arrays, as well as methods for sampling tissues and assessing lung function in the horse are constantly evolving to facilitate the study of this animal model. Research perspectives that can be relevant to asthma include the role of neutrophils in airway inflammation and their response to corticosteroids, systemic response to pulmonary inflammation, and maintaining athletic capacities with early intervention.
Recent studies suggest that airway smooth muscle remodeling is an early event in the course of asthma. Little is known of the effects of long-term antigen avoidance and inhaled corticosteroids on chronically established airway remodeling. We sought to measure the effects of inhaled corticosteroids and antigen avoidance on airway remodeling in the peripheral airways of horses with heaves, a naturally occurring asthma-like disease. Heaves-affected adult horses with ongoing airway inflammation and bronchoconstriction were treated with fluticasone propionate (with and without concurrent antigen avoidance) (n = 6) or with antigen avoidance alone (n = 5). Lung function and bronchoalveolar lavage were performed at multiple time points, and peripheral lung biopsies were collected before and after 6 and 12 months of treatment. Lung function improved more quickly with inhaled corticosteroids, but eventually normalized in both groups. Inflammation was better controlled with antigen avoidance. During the study period, corrected smooth muscle mass decreased from 12.1 ± 2.8 × 10(-3) and 11.3 ± 1.2 × 10(-3) to 8.3 ± 1.4 × 10(-3) and 7.9 ± 1.0 × 10(-3) in the antigen avoidance and fluticasone groups, respectively (P = 0.03). At 6 months, smooth muscle mass was significantly smaller compared with baseline only in the fluticasone-treated animals. The subepithelial collagen area was lower at 12 months than at baseline in both groups. During the study period, airway smooth muscle remodeling decreased by approximately 30% in both groups, although the decrease was faster in horses receiving inhaled corticosteroids. Inhaled corticosteroids may accelerate the reversal of smooth muscle remodeling, even if airway inflammation is better controlled with antigen avoidance.
Recent studies suggest that airway smooth muscle remodeling is an early event in asthma, but whether it remains a dynamic process late in the course of the disease is unknown. Moreover, little is known about the effects of an antigenic exposure on chronically established smooth muscle remodeling. We measured the effects of antigenic exposure on airway smooth muscle in the central and peripheral airways of horses with heaves, a naturally occurring airway disease that shares similarities with chronic asthma. Heaves-affected horses (n = 6) and age-matched control horses (n = 5) were kept on pasture before being exposed to indoor antigens for 30 days to induce airway inflammation and bronchoconstriction. Peripheral lung and endobronchial biopsies were collected before and after antigenic exposure by thoracoscopy and bronchoscopy, respectively. Immunohistochemistry and enzymatic labeling were used for morphometric analyses of airway smooth muscle mass and proliferative and apoptotic myocytes. In the peripheral airways, heaves-affected horses had twice as much smooth muscle as control horses. Remodeling was associated with smooth muscle hyperplasia and in situ proliferation, without reduced apoptosis. Further antigenic exposure had no effect on the morphometric data. In central airways, proliferating myocytes were increased compared with control horses only after antigenic exposure. Peripheral airway smooth muscle mass is stable in chronically affected animals subjected to antigenic exposure. This increased mass is maintained in a dynamic equilibrium by an elevated cellular turnover, suggesting that targeting smooth muscle proliferation could be effective at decreasing chronic remodeling.
2The main factors regulating grapevine response to decreasing water availability were assessed under statistical support using published data related to leaf water relations in an extensive range of scion and rootstock genotypes.Matching Ψ leaf and g s data were collected from peer-reviewed literature with associated information. The resulting database contained 718 data points from 26 different Vitis vinifera varieties investigated as scions, 15 non-V.vinifera rootstock genotypes and 11 own-rooted V. vinifera varieties. Linearized data were analyzed using the univariate general linear model (GLM) with factorial design including biological (scion and rootstock genotypes), methodological and environmental (soil) fixed factors.The first GLM performed on the whole database explained 82.4% of the variability in data distribution having the rootstock genotype the greatest contribution to variability (19.1%) followed by the scion genotype (16.2%). A classification of scions and rootstocks according to their mean predicted g s in response to moderate water stress was generated. This model also revealed that g s data obtained using a porometer were in average 2.1 times higher than using an infra-red gas analyser. The effect of soil waterholding properties was evaluated in a second analysis on a restricted database and showed a sciondependant effect, which was dominant over rootstock effect, in predicting g s values.Overall the results suggest that a continuum exists in the range of stomatal sensitivities to water stress in V. vinifera, rather than an isohydric-anisohydric dichotomy, that is further enriched by the diversity of scion-rootstock combinations and their interaction with different soils.Key words: scion, rootstock, isohydric, anisohydric, Vitis, water potential Abbreviations ABA, absisic acid; A N,, net assimilation of CO 2 ; g s,, stomatal conductance; IRGA, infra-red gas analyser; PRD, partial root drying; WUE, water use efficiency; Ψ leaf , leaf water potential; Ψ stem , stem water potential. 3 IntroductionFurther decrease in water availability is predicted in some important viticulture areas such as the Mediterranean basin as a consequence of increased atmospheric green gas emissions and associated rise in surface temperatures (IPCC 2014). These climatic changes would lead to increased atmospheric water demand and consequently to an increased rate of crop evapotranspiration and soil water depletion.Excessive water limitation impairs plant growth and consequently the amount of exposed leaf area, compromising the maturation of fruit and on the long term the carbon balance of the crop and its lifespan.These represent a major threat to the wine industry sector for which major agronomical and enological adaptations will be required to sustain its activity. Although irrigation could be considered as a solving option, it is not a sustainable one in many viticulture settings.Efforts have been made to better understand the mechanisms of water use efficiency (WUE) in grapevine (Flexas et al. 2016). Adapting viticul...
Grapevine adaptations to water-stress are described, by focusing on soil/root interactions and root-to-shoot signaling to control both plant water relations and fruit ripening process.Root response to drought, tolerance of available rootstock germoplasm, mechanisms of embolism formation and repair in root, aquaporin control of plant water relations, and abscisic acid biosynthesis and delivery are highlighted, by reviewing recent insights coming from either (eco)physiological literature or viticultural assays addressing vineyard-soil relationships.
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