Immune deficiencies, infection, and systemic immune disorders
Exposure to welding fumes and lower airway infection with Streptococcus pneumoniae

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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.

Section snippets

WF: Generation and composition

MS-WF were a gift from the Welding Institute (Cambridge, UK). MS-WF were obtained by using a standardized method in accordance with the International Standard 15011-1:2009, as previously described.17 Briefly, manual metal arc welding electrodes (mild steel E7018 basic type) were run to produce a weld bead inside a fume collection system. MS-WF with a mode particle diameter of 6.8 μm18 were extracted through the hood on top of the box, collected on a filter paper, removed by brushing, and stored

WF: OP

MS-WF contained iron, manganese, titanium, aluminum, and zinc (Table I). The OP of MW-WF for ascorbate and glutathione was increased compared with that of carbon black, and the total OP of MS-WF was increased compared with that of urban PM (Fig 1).

Pneumococcal adhesion and infection: Human airway cells

We first performed dose-response experiments with A549 and BEAS-2B cells to determine the optimal concentration of MS-WF that stimulated adhesion without causing cytotoxicity. MS-WF at concentrations between 200 and 400 μg/mL for 2 hours increased

Discussion

In this study we sought to identify a mechanism for the hypersusceptibility of welders to bacterial pneumonia reported in epidemiologic studies.2, 4, 24 We focused on S pneumoniae because this bacterium is the most common cause of community-acquired pneumonia in adults.10 In addition, a review of all patients presenting with invasive pneumococcal disease (IPD) in Alberta (Canada) from 2000 to 2004 by Wong et al25 reported a 2.7-fold greater incidence of IPD in welders; of the 18 welders with

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    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.

    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.

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