An Adverse Outcome Pathway for Decreased Lung Function Focusing on Mechanisms of Impaired Mucociliary Clearance Following Inhalation Exposure

Frontiers in Toxicology

Monita Sharma¹  Frazer J. Lowe¹  Hasmik Yepiskoposyan²  Karsta Luettich³  Damien Breheny³ 

[1] D, Philip Morris Products S.A., Neuchatel, Switzerland;PETA Science Consortium International e.V., Stuttgart, Germany;;Philip Morris International R&

关键词: adverse outcome pathway;    AOP;    mucociliary clearance;    ciliary beat frequency;    lung function;    new approach methodologies;   

DOI  :  10.3389/ftox.2021.750254

来源: DOAJ

【 摘 要 】

Adverse outcome pathways (AOPs) help to organize available mechanistic information related to an adverse outcome into key events (KEs) spanning all organizational levels of a biological system(s). AOPs, therefore, aid in the biological understanding of a particular pathogenesis and also help with linking exposures to eventual toxic effects. In the regulatory context, knowledge of disease mechanisms can help design testing strategies using in vitro methods that can measure or predict KEs relevant to the biological effect of interest. The AOP described here evaluates the major processes known to be involved in regulating efficient mucociliary clearance (MCC) following exposures causing oxidative stress. MCC is a key aspect of the innate immune defense against airborne pathogens and inhaled chemicals and is governed by the concerted action of its functional components, the cilia and airway surface liquid (ASL). The AOP network described here consists of sequences of KEs that culminate in the modulation of ciliary beat frequency and ASL height as well as mucus viscosity and hence, impairment of MCC, which in turn leads to decreased lung function.

【 授权许可】

Unknown