The changing role of eosinophils in long-term hyperreactivity following a single ozone exposure

2005 ◽  
Vol 289 (4) ◽  
pp. L627-L635 ◽  
Author(s):  
Bethany L. Yost ◽  
Gerald J. Gleich ◽  
David B. Jacoby ◽  
Allison D. Fryer
Keyword(s):  
Smooth Muscle ◽  
Vagal Stimulation ◽  
Airway Hyperreactivity ◽  
Ozone Exposure ◽  
Single Exposure ◽  
Eosinophil Major Basic Protein ◽  
Changing Role ◽  
Eosinophil Accumulation

Ozone hyperreactivity over 24 h is mediated by blockade of inhibitory M2 muscarinic autoreceptors by eosinophil major basic protein. Because eosinophil populations in the lungs fluctuate following ozone, the contribution of eosinophils to M2 dysfunction and airway hyperreactivity was measured over several days. After one exposure to ozone, M2 function, vagal reactivity, smooth muscle responsiveness, and inflammation were measured in anesthetized guinea pigs. Ozone-induced hyperreactivity to vagal stimulation persisted over 3 days. Although hyperreactivity one day after ozone is mediated by eosinophils, AbVLA-4 did not inhibit either eosinophil accumulation in the lungs or around the nerves or prevent hyperreactivity at this time point. Two days after ozone, eosinophils in BAL, around airway nerves and in lungs, were decreased, and neuronal M2 receptor function was normal, although animals were still hyperreactive to vagal stimulation. Depleting eosinophils with AbIL-5 prevented hyperreactivity, thus eosinophils contribute to vagal hyperreactivity by mechanisms separate from M2 receptor blockade. Three days after ozone, vagal hyperreactivity persisted, eosinophils were again elevated in BAL in lungs and around nerves, and M2 receptors were again dysfunctional. At this point, airway smooth muscle was also hyperresponsive to methacholine. Eosinophil depletion with AbIL-5, AbVLA-4, or cyclophosphamide protected M2 function 3 days after ozone and prevented smooth muscle hyperreactivity. However, vagal hyperreactivity was significantly potentiated by eosinophil depletion. The site of hyperreactivity, muscle or nerve, changes over 3 days after a single exposure to ozone. Additionally, the role of eosinophils is complex; they mediate hyperreactivity acutely while chronically may be involved in repair.

scholarly journals Three days after a single exposure to ozone, the mechanism of airway hyperreactivity is dependent on substance P and nerve growth factor

2011 ◽  
Vol 300 (2) ◽  
pp. L176-L184 ◽  
Author(s):  
Kirsten C. Verhein ◽  
Mehdi S. Hazari ◽  
Bart C. Moulton ◽  
Isabella W. Jacoby ◽  
David B. Jacoby ◽  
...  
Keyword(s):  
Substance P ◽  
Neural Plasticity ◽  
Guinea Pigs ◽  
Acetylcholine Release ◽  
Basic Protein ◽  
Smooth Muscle Contraction ◽  
Airway Hyperreactivity ◽  
Ozone Exposure ◽  
Single Exposure ◽  
Eosinophil Major Basic Protein

Ozone causes persistent airway hyperreactivity in humans and animals. One day after ozone exposure, airway hyperreactivity is mediated by release of eosinophil major basic protein that inhibits neuronal M2 muscarinic receptors, resulting in increased acetylcholine release and increased smooth muscle contraction in guinea pigs. Three days after ozone, IL-1β, not eosinophils, mediates ozone-induced airway hyperreactivity, but the mechanism at this time point is largely unknown. IL-1β increases NGF and the tachykinin substance P, both of which are involved in neural plasticity. These experiments were designed to test whether there is a role for NGF and tachykinins in sustained airway hyperreactivity following a single ozone exposure. Guinea pigs were exposed to filtered air or ozone (2 parts per million, 4 h). In anesthetized and vagotomized animals, ozone potentiated vagally mediated airway hyperreactivity 24 h later, an effect that was sustained over 3 days. Pretreatment with antibody to NGF completely prevented ozone-induced airway hyperreactivity 3 days, but not 1 day, after ozone and significantly reduced the number of substance P-positive airway nerve bundles. Three days after ozone, NK1 and NK2 receptor antagonists also blocked this sustained hyperreactivity. Although the effect of inhibiting NK2 receptors was independent of ozone, the NK1 receptor antagonist selectively blocked vagal hyperreactivity 3 days after ozone. These data confirm mechanisms of ozone-induced airway hyperreactivity change over time and demonstrate 3 days after ozone that there is an NGF-mediated role for substance P, or another NK1 receptor agonist, that enhances acetylcholine release and was not present 1 day after ozone.

Review Lecture - Ore-deposition through geological time

1978 ◽  
Vol 362 (1710) ◽  
pp. 305-328 ◽  
Keyword(s):  
Mineral Deposits ◽  
Banded Iron Formations ◽  
Geological Time ◽  
The Earth ◽  
Recent Developments ◽  
Changing Role ◽  
Iron Formations ◽  
Ore Deposition

Economic mineral deposits represent abnormal concentrations of metals which must be regarded as records of unusual geological events. The recognition of any long-term changes in styles of mineralization must depend on the identification of anomalies within the geological régimes characteristic of successive stages of the Earth’s history. This question will be discussed in relation to recent developments in the Earth sciences. The recognition of structural and chemical inhomogeneities in the lithospheric mantle suggests that mapping of mantle age-provinces may become possible; such studies bear on the significance of certain metallogenic provinces. Coordinated geochemical, structural and palaeomagnetic studies which are throwing light on the evolution of early tectonic systems should help to illuminate the significance of changes in style of mineralization at the Archaean/Proterozoic boundary, as well as the distribution of some types of Proterozoic deposits. Geochemical evidence concerning the changing rôle of organic processes in sedimentation and diagenesis has a bearing on the origin of sedimentary ores, especially over the controversial period characterized by accumulation of banded iron-formations.

scholarly journals Long-term retrospective trends in the EU foreign trade development with the UK, USA and China

2020 ◽  
pp. 23-43
Author(s):  
L. L. Razumnova
Keyword(s):  
Foreign Trade ◽  
The United States ◽  
The European Union ◽  
Trade Turnover ◽  
The Uk ◽  
Foreign Trade Turnover ◽  
Quantitative Indicators ◽  
Changing Role

Based on the latest data, the article examines the quantitative indicators of foreign trade in goods of the European Union (EU27) over the past 15 years with states that are not part of this economic grouping. Trends in the structure and dynamics of foreign trade turnover are revealed, including those determined by changing role of Great Britain and the United States in connection with Britain's secession from the Union (Brexit) in January 2020. In particular, there is a convergence in the growth rates of the studied countries group and an increase in its share in EU imports while reducing the share in merchandise exports. The quantitative trends of changes in the trade balance and commodity structure are analyzed. The author identifies the most significant factors determining the development of EU commodity exchange, comprising the role of US oil exports and anti-Russian sanctions. Some promising areas of research on this issue are determined with consideration of the results obtained by Russian and foreign scientists, such as competitiveness and the formation of the global value chains.

Atropine pretreatment enhances airway hyperreactivity in antigen-challenged guinea pigs through an eosinophil-dependent mechanism

2007 ◽  
Vol 292 (5) ◽  
pp. L1126-L1135 ◽  
Author(s):  
Norah G. Verbout ◽  
Jesse K. Lorton ◽  
David B. Jacoby ◽  
Allison D. Fryer
Keyword(s):  
Muscarinic Receptors ◽  
Guinea Pigs ◽  
Airway Hyperreactivity ◽  
Antigen Challenge ◽  
Receptor Function ◽  
Airway Reactivity ◽  
Parasympathetic Nerves ◽  
Eosinophil Activation ◽  
Eosinophil Major Basic Protein ◽  
Eosinophil Accumulation

Airway hyperreactivity in antigen-challenged animals is mediated by eosinophil major basic protein (MBP) that blocks inhibitory M2 muscarinic receptors on parasympathetic nerves, increasing acetylcholine release onto M3 muscarinic receptors on airway smooth muscle. Acutely, anticholinergics block hyperreactivity in antigen-challenged animals and reverse asthma exacerbations in the human, but are less effective in chronic asthma. We tested whether atropine, given before antigen challenge, affected hyperreactivity, M2 receptor function, eosinophil accumulation, and activation. Sensitized guinea pigs received atropine (1 mg/kg ip) 1 h before challenge and 6 h later. Twenty-four hours after challenge, animals were anesthetized, vagotomized, paralyzed, and ventilated. Airway reactivity to electrical stimulation of the vagi and to intravenous acetylcholine was not altered by atropine pretreatment in nonsensitized animals, indicating that atropine was no longer blocking postjunctional muscarinic receptors. Antigen challenge induced airway hyperreactivity to vagal stimulation that was significantly potentiated by atropine pretreatment. Bronchoconstriction induced by acetylcholine was not changed by antigen challenge or by atropine pretreatment. M2 receptor function was lost in challenged animals but protected by atropine pretreatment. Eosinophils in bronchoalveolar lavage and within airway tissues were significantly increased by challenge but significantly reduced by atropine pretreatment. However, extracellular MBP in challenged airways was significantly increased by atropine pretreatment, which may account for reduced eosinophils. Depleting eosinophils with antibody to IL-5 before challenge prevented hyperreactivity and significantly reduced MBP in airways of atropine-pretreated animals. Thus atropine pretreatment potentiated airway hyperreactivity by increasing eosinophil activation and degranulation. These data suggest that anticholinergics enhance eosinophil interactions with airway nerves.

Becoming a Swarm Catalyst

2013 ◽  
Vol 3 (1) ◽  
pp. 57-70 ◽  
Author(s):  
Juhana Kokkonen ◽  
Sami Paavola ◽  
Yrjö Engeström
Keyword(s):  
Applied Sciences ◽  
Social Media ◽  
Development Process ◽  
Hierarchical Organization ◽  
Collaborative Community ◽  
University Of Applied Sciences ◽  
Traditional Organization ◽  
Changing Role

This article analyzes the problems of bringing in social media in a traditional, hierarchical organization. Difficulties rise from the contradiction between the bureaucratic approach of an organization and the collaborative community approach connected to social media. A change in the role of a developer is analyzed through a case study. The data was collected in a co-development process of a work unit at a Finnish University of Applied Sciences. The method of this study is analytic autoethnography, which proved to be a valuable tool for capturing a long-term development process and the changing role of the developer inside the organization. A new change agent, a swarm catalyst, is introduced at the end of the article. The initial characteristics of a swarm catalyst are based on the experiences of various, iterative developmental experiments. A swarm catalyst operates within an organization as an autonomous developer, and as a negotiator between the traditional organization and decentralized developmental swarms.

Long-term regulation of Na(+)-H+ exchange in vascular smooth muscle cells: role of protein kinase C

1991 ◽  
Vol 260 (3) ◽  
pp. C562-C569 ◽  
Author(s):  
M. Mitsuka ◽  
B. C. Berk
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Vascular Smooth Muscle ◽  
Kinetic Properties ◽  
Dependent Manner ◽  
Kinase C ◽  
Measured Exposure

Regulation of intracellular pH (pHi) plays an important role in vascular smooth muscle cell (VSMC) contractile tone and growth. We have shown that pHi in proliferating VSMC is more alkaline (7.25) than in growth-arrested cells (7.10). To study the Na(+)-H+ exchanger in the growth-dependent regulation of VSMC pHi, ethylisopropylamiloride (EIPA)-sensitive Na+ influx was measured. Exposure of growth-arrested VSMC to 10% serum initially increased Na+ influx (145% of baseline at 30 min), which then decreased (52% of baseline at 24 h). Serum-induced alterations in the kinetic properties of the Na(+)-H+ exchanger were studied by analysis of its external Na+ binding site properties. Exposure of growth-arrested VSMC to 10% serum for 24 h increased the Km for external Na+ from 54 to 380 mM, with a change in the Vmax from 155 to 199 nmol Na+.mg protein-1.min-1. The change in Km was due to activation of protein kinase C (PKC). Phorbol 12,13-dibutyrate caused a 48% decrease in EIPA-sensitive influx, the inactive 4 alpha-phorbol 12,13-didecanoate had no effect, and the PKC inhibitor sphingosine reversed the effect. Therefore, the Na(+)-H+ exchanger in VSMC is regulated in a growth-dependent manner via PKC.

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