Exposure to welding fumes and lower airway infection with Streptococcus pneumoniae.
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.
Blizard Institute, Queen Mary University of London, London, United Kingdom.
Reetika
R
Suri
Centre for Inflammation and Tissue Repair, Department of Medicine, Royal Free and University College Medical School, Rayne Institute, London, United Kingdom.
Jimstan
J
Periselneris
Inserm U955 Équipe 4, Faculté de Médecine, Créteil, France.
Sophie
S
Lanone
Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV.
Patti C
PC
Zeidler-Erdely
Welding Institute, Cambridge, United Kingdom.
Geoffrey
G
Melton
MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, United Kingdom.
Keith T
KT
Palmer
Inserm U955 Équipe 4, Faculté de Médecine, Créteil, France.
Pascal
P
Andujar
Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV.
James M
JM
Antonini
Inserm U955 Équipe 4, Faculté de Médecine, Créteil, France.
Vanessa
V
Cohignac
Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV.
Aaron
A
Erdely
Centre for Inflammation and Tissue Repair, Department of Medicine, Royal Free and University College Medical School, Rayne Institute, London, United Kingdom.
Ricardo J
RJ
Jose
MRC-PHE Centre for Environment and Health, Analytical & Environmental Sciences Division, Faculty of Life Sciences & Medicine, King's College London, London, United Kingdom.
Ian
I
Mudway
Centre for Inflammation and Tissue Repair, Department of Medicine, Royal Free and University College Medical School, Rayne Institute, London, United Kingdom.
Jeremy
J
Brown
Blizard Institute, Queen Mary University of London, London, United Kingdom. Electronic address: j.grigg@qmul.ac.uk.
Jonathan
J
Grigg
D000818:Animals; D001422:Bacterial Adhesion; D058491:Bacterial Load; D001992:Bronchoalveolar Lavage Fluid; D002460:Cell Line; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005260:Female; D015870:Gene Expression; D000075322:Heavy Metal Poisoning; D006801:Humans; D051379:Mice; D016273:Occupational Exposure / Q000009:adverse effects*; D018384:Oxidative Stress; D010980:Platelet Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D011018:Pneumonia, Pneumococcal / Q000209:etiology* / Q000378:metabolism / Q000382:microbiology*; D011041:Poisoning; D012333:RNA, Messenger / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D013296:Streptococcus pneumoniae; D014896:Welding
D010980:Platelet Membrane Glycoproteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor
Occupational disease; Streptococcus pneumoniae; bacterial adhesion and infection; platelet-activating factor receptor; pneumonia; welding fumes