0
Correspondence |

ResponseResponse FREE TO VIEW

Claire M. Smith, PhD; Robert A. Hirst, PhD; Christopher O’Callaghan, DM, PhD
Author and Funding Information

From the Department of Respiratory Medicine, Portex Unit, Institute of Child Health, UCL, and Great Ormond Street Hospital for Children NHS Foundation Trust (Dr Smith and Prof O’Callaghan); and Department of Infection, Immunity and Inflammation (Dr Hirst), University of Leicester.

Correspondence to: Christopher O’Callaghan, DM, PhD, Department of Respiratory Medicine, Portex Unit, Institute of Child Health, UCL, 30 Guilford St, London, WC1N 1EH, England; e-mail: c.ocallaghan@ucl.ac.uk


Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;145(3):669. doi:10.1378/chest.14-0187
Text Size: A A A
Published online
To the Editor:

We read with interest the letter by Dr Walker and colleagues that addresses the important issue of the regulation of nitric oxide (NO) biosynthesis in patients with primary ciliary dyskinesia (PCD). The authors analyzed NO production in primary ciliated epithelial cell cultures from patients with PCD at baseline and 72 h after coculture with Haemophilus influenzae and found an increase in NO production. It is important to highlight that our findings published in CHEST1 conflict with this report. We originally described how the coculture of ciliated epithelial cells from patients with PCD with Streptococcus pneumoniae (for 2 h) was associated with defective NO production compared with cell cultures from healthy volunteers that increased NO production.1

These conflicting datasets may be due to differences in the mechanism of infection and cytotoxicology in air-liquid interface cultures between the two microorganisms. We have previously shown that S pneumoniae release the cytolytic toxin pneumolysin, and this causes widespread destruction to the ciliated epithelium.2 For this reason, it would be impossible to test the NO production at 72 h after pneumococcal infection.

The authors also did not investigate nitric oxide synthase (NOS) expression and failed to describe the PCD phenotype of the subjects/cells used. This information may also explain the conflicting findings. In healthy epithelial cells, NO is believed to be produced in response to infection by inducible NOS,3 which is expressed by the NOS2 gene in the respiratory tract. We showed that the NO production in PCD is linked to defective NOS2 expression, which remained unchanged from baseline. It is possible that the increased levels of NO seen in PCD cell cultures observed 72 h after infection with Haemophilus may be a result of upregulation of NO production, increased protein expression by NOS enzymes other than inducible NOS, or both.

We believe that the analysis of ciliary activity and NO production during the early time points of infection is of key importance in studying the biosynthesis of NO in the respiratory epithelium of patients with PCD. This work is currently being undertaken.

References

Smith CM, Fadaee-Shohada MJ, Sawhney R, et al. Ciliated cultures from patients with primary ciliary dyskinesia do not produce nitric oxide or inducible nitric oxide synthase during early infection. Chest. 2013;144(5):1671-1676. [CrossRef] [PubMed]
 
Hirst RA, Sikand KS, Rutman A, Mitchell TJ, Andrew PW, O’Callaghan C. Relative roles of pneumolysin and hydrogen peroxide fromStreptococcus pneumoniaein inhibition of ependymal ciliary beat frequency. Infect Immun. 2000;68(3):1557-1562. [CrossRef] [PubMed]
 
Moncada S, Higgs A. The L-arginine-nitric oxide pathway. N Engl J Med. 1993;329(27):2002-2012. [CrossRef] [PubMed]
 

Figures

Tables

References

Smith CM, Fadaee-Shohada MJ, Sawhney R, et al. Ciliated cultures from patients with primary ciliary dyskinesia do not produce nitric oxide or inducible nitric oxide synthase during early infection. Chest. 2013;144(5):1671-1676. [CrossRef] [PubMed]
 
Hirst RA, Sikand KS, Rutman A, Mitchell TJ, Andrew PW, O’Callaghan C. Relative roles of pneumolysin and hydrogen peroxide fromStreptococcus pneumoniaein inhibition of ependymal ciliary beat frequency. Infect Immun. 2000;68(3):1557-1562. [CrossRef] [PubMed]
 
Moncada S, Higgs A. The L-arginine-nitric oxide pathway. N Engl J Med. 1993;329(27):2002-2012. [CrossRef] [PubMed]
 
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543