Exposure to welding fumes and lower airway infection with Streptococcus pneumoniae - 05/02/16
Abstract |
Background |
Welders are at increased risk of pneumococcal pneumonia. The mechanism for this association is not known. The capacity of pneumococci to adhere to and infect lower airway cells is mediated by host-expressed platelet-activating factor receptor (PAFR).
Objective |
We sought to assess the effect of mild steel welding fumes (MS-WF) on PAFR-dependent pneumococcal adhesion and infection to human airway cells in vitro and on pneumococcal airway infection in a mouse model.
Methods |
The oxidative potential of MS-WF was assessed by their capacity to reduce antioxidants in vitro. Pneumococcal adhesion and infection of A549, BEAS-2B, and primary human bronchial airway cells were assessed by means of quantitative bacterial culture and expressed as colony-forming units (CFU). After intranasal instillation of MS-WF, mice were infected with Streptococcus pneumoniae, and bronchoalveolar lavage fluid (BALF) and lung CFU values were determined. PAFR protein levels were assessed by using immunofluorescence and immunohistochemistry, and PAFR mRNA expression was assessed by using quantitative PCR. PAFR was blocked by CV-3988, and oxidative stress was attenuated by N-acetylcysteine.
Results |
MS-WF exhibited high oxidative potential. In A549 and BEAS-2B cells MS-WF increased pneumococcal adhesion and infection and PAFR protein expression. Both CV-3988 and N-acetylcysteine reduced MS-WF–stimulated pneumococcal adhesion and infection of airway cells. MS-WF increased mouse lung PAFR mRNA expression and increased BALF and lung pneumococcal CFU values. In MS-WF–exposed mice CV-3988 reduced BALF CFU values.
Conclusions |
Hypersusceptibility of welders to pneumococcal pneumonia is in part mediated by the capacity of welding fumes to increase PAFR-dependent pneumococcal adhesion and infection of lower airway cells.
Le texte complet de cet article est disponible en PDF.Key words : Occupational disease, welding fumes, platelet-activating factor receptor, Streptococcus pneumoniae, pneumonia, bacterial adhesion and infection
Abbreviations used : BALF, CFU, IPD, LDH, MS-WF, NAC, OP, PAFR, PM, StS-WF, UK, WF
Plan
| Supported by Colt Foundation grant number CF/05/12. R.J.J. is supported by Wellcome Trust grant 097216/Z/11/Z, and J.P. is supported by Medical Research Council grant MR/K00168X/1. |
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| Disclosure of potential conflict of interest: G. Melton is exclusively funded by the Welding Institute (an independent research organization, limited by guarantee), which is funded by member subscriptions (about 800 members worldwide), single-client and joint industry projects, and European Union– and United Kingdom–funded projects. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 137 - N° 2
P. 527 - février 2016 Retour au numéro
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