Suri, R;
Periselneris, J;
Lanone, S;
Zeidler-Erdely, PC;
Melton, G;
Palmer, KT;
Andujar, P;
... Grigg, J; + view all
(2015)
Exposure to welding fumes and lower airway infection with Streptococcus pneumoniae.
Journal of Allergy and Clinical Immunology
, 137
(2)
527-534.e7.
10.1016/j.jaci.2015.06.033.
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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.
| Type: | Article |
|---|---|
| Title: | Exposure to welding fumes and lower airway infection with Streptococcus pneumoniae |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.jaci.2015.06.033 |
| Publisher version: | https://doi.org/10.1016/j.jaci.2015.06.033 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Allergy, Immunology, Occupational disease, welding fumes, platelet-activating factor receptor, Streptococcus pneumoniae, pneumonia, bacterial adhesion and infection, PLATELET-ACTIVATING-FACTOR, OBSTRUCTIVE PULMONARY-DISEASE, FACTOR RECEPTOR, INHALATION EXPOSURE, DEFENSE RESPONSES, PNEUMOCOCCAL PNEUMONIA, LUNG INFLAMMATION, CIGARETTE-SMOKE, IN-VITRO, CELLS |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Respiratory Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10043062 |
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