Abstract：
:Pathogenic granulocytes (eosinophils and neutrophils) infiltrate airway tissues in asthma and chronic obstructive pulmonary disease. Granulocytes release tissue-toxic and inflammatory mediators, making their removal an important pharmacological goal. Removal is thought to be accomplished through apoptosis followed by engulfment by macrophages. Thus, the molecular mechanisms of granulocyte apoptosis have been unravelled and pro-apoptotic actions that target granulocytes have been proposed as desirable features of future airway drugs. However, observations in vitro and in airway lumen that support this role of granulocyte apoptosis translate poorly to airway tissues in vivo. Either apoptosis cannot be demonstrated, even at the resolution of airway inflammation, or, when significant granulocyte apoptosis is induced in airway tissues in vivo, there is insufficient engulfment of apoptotic granulocytes. Therefore, apoptotic eosinophils and neutrophils in airway tissues undergo secondary necrosis, causing inflammation. As an alternative or complement to the apoptosis hypothesis, in vivo work indicates that egression to the airway lumen can produce swift non-injurious removal of tissue granulocytes. Once in the airway lumen, granulocytes can undergo apoptosis and engulfment, be trapped by secretions and plasma exudates and be removed by mucociliary escalator mechanisms. In this article, we propose that egression into the airway lumen is an effective mode of inflammatory cell disposal that connotes novel drug opportunities.
journal_name
Trends Pharmacol Scijournal_title
Trends in pharmacological sciencesauthors
Uller L,Persson CG,Erjefält JSdoi
10.1016/j.tips.2006.07.006subject
Has Abstractpub_date
2006-09-01 00:00:00pages
461-6issue
9eissn
0165-6147issn
1873-3735pii
S0165-6147(06)00177-5journal_volume
27pub_type
杂志文章abstract：:Platelet activating factor (PAF) is a phospholipid mediator of inflammation and stimulates anion secretion in animals and in isolated preparations of human colon. Nitric oxide (NO), synthesized from the amino acid L-arginine, is an important enteric inhibitory neurotransmitter. In addition, NO-donating compounds stimu...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(98)01249-8
更新日期：1998-10-01 00:00:00
abstract：:The 5-HT7 receptor was among a group of 5-HT receptors that were discovered using targeted cloning strategies 12 years ago. This receptor is a seven-transmembrane-domain G-protein-coupled receptor that is positively linked to adenylyl cyclase. The distributions of 5-HT7 receptor mRNA, immunolabeling and radioligand bi...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
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abstract：:The discovery of neuropeptides as signaling molecules with paracrine or hormonal regulatory functions has led to trailblazing advances in physiology and fostered the characterization of numerous neuropeptide-binding G protein-coupled receptors (GPCRs) as potential drug targets. The impact on human health has been trem...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
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journal_title：Trends in pharmacological sciences
pub_type： 评论,杂志文章
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journal_title：Trends in pharmacological sciences
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pub_type： 杂志文章,评审
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更新日期：2021-01-23 00:00:00
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journal_title：Trends in pharmacological sciences
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更新日期：2000-05-01 00:00:00
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.tips.2007.03.003
更新日期：2007-05-01 00:00:00
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2009.07.001
更新日期：2009-10-01 00:00:00
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(00)89066-5
更新日期：1995-10-01 00:00:00
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
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更新日期：2016-07-01 00:00:00
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(98)01261-9
更新日期：1998-11-01 00:00:00
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2018.10.008
更新日期：2019-01-01 00:00:00
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
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更新日期：2000-01-01 00:00:00
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2015.05.006
更新日期：2015-08-01 00:00:00
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journal_title：Trends in pharmacological sciences
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更新日期：1999-12-01 00:00:00
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journal_title：Trends in pharmacological sciences
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更新日期：2001-04-01 00:00:00
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journal_title：Trends in pharmacological sciences
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更新日期：2008-10-01 00:00:00
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journal_title：Trends in pharmacological sciences
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更新日期：2012-10-01 00:00:00
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journal_title：Trends in pharmacological sciences
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更新日期：2002-08-01 00:00:00
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
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更新日期：2007-03-01 00:00:00
abstract：:NMDA and non-NMDA (AMPA/kainate) antagonists have potential in the treatment of a diverse group of neurological disorders associated with excessive activation of excitatory amino acid receptors. Here Michael Rogawski reviews recent progress in the development of therapeutically useful NMDA receptor channel blockers an...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/0165-6147(93)90005-5
更新日期：1993-09-01 00:00:00
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
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更新日期：2006-09-01 00:00:00
abstract：:During the past decade, translocator protein 18 kDa (TSPO), previously named peripheral benzodiazepine receptor, has gained a great deal of attention based on its use as a clinical biomarker of neuroinflammation with therapeutic potential. However, there is a paucity of knowledge on the function(s) of TSPO in glial ce...
journal_title：Trends in pharmacological sciences
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更新日期：2016-05-01 00:00:00
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
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更新日期：2014-12-01 00:00:00
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journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
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更新日期：2016-08-01 00:00:00
abstract：:Apoptosis plays a key role in tumour biology, and the induction of apoptosis forms a cornerstone of most anticancer therapies. New developments in nuclear magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) have taken these techniques far beyond their original roles as the workhorses of structur...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/S0165-6147(03)00032-4
更新日期：2003-03-01 00:00:00
