Abstract:
:Infection of the cystic fibrosis (CF) airways elicits an exaggerated, interleukin-8 (IL-8) mediated, neutrophil inflammatory response. Necrosing neutrophils release DNA and actin into the airways, increasing the viscoelasticity of airway secretions. Mucolytics aim to improve airway clearance by reducing this viscoelasticity. DNase I reduces the viscoelasticity of CF sputum, and a human recombinant form of this enzyme is widely administered to patients with CF. Gelsolin, which cleaves actin polymers, is also known to reduce CF sputum viscosity in vitro, and it has been proposed as a future mucolytic agent. We have shown that the anionic polymers DNA and actin bind and mask immunologic recognition of the basic peptide IL-8 and prevent this chemokine from binding to neutrophil receptors. Reduction of CF sputum viscosity by DNase I or gelsolin in vitro was demonstrated to increase the proportion of free IL-8 and the IL-8-dependent neutrophil chemotactic activity of sputum supernatants. We hypothesize that an electrostatic interaction between polymer and chemokine may limit the inflammatory potential of the latter, but that this interaction may be weakened by polymer cleavage. The potential risk of increased inflammation via this mechanism suggests a caveat should be attendant on treatment of patients with CF with these mucolytic agents.
journal_name
Am J Respir Crit Care Medauthors
Perks B,Shute JKdoi
10.1164/ajrccm.162.5.9908107keywords:
subject
Has Abstractpub_date
2000-11-01 00:00:00pages
1767-72issue
5eissn
1073-449Xissn
1535-4970journal_volume
162pub_type
杂志文章abstract:RATIONALE:The allergen inhalation challenge is used in clinical trials to test the efficacy of new treatments in attenuating the late-phase asthmatic response (LAR) and associated airway inflammation in subjects with allergic asthma. However, not all subjects with allergic asthma develop the LAR after allergen inhalati...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
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更新日期:2018-02-15 00:00:00
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pub_type: 临床试验,杂志文章
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journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2011-08-15 00:00:00
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pub_type: 杂志文章
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更新日期:1994-12-01 00:00:00
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pub_type: 杂志文章,多中心研究
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更新日期:2002-03-15 00:00:00
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更新日期:2000-05-01 00:00:00
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pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2015-06-01 00:00:00
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更新日期:2011-03-01 00:00:00
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pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2010-01-01 00:00:00
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journal_title:American journal of respiratory and critical care medicine
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更新日期:1997-07-01 00:00:00
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更新日期:2008-02-15 00:00:00
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pub_type: 临床试验,杂志文章
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更新日期:2008-04-01 00:00:00
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journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
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更新日期:2004-09-01 00:00:00