Abnormal nasal nitric oxide production, ciliary beat frequency, and Toll-like receptor response in pulmonary nontuberculous mycobacterial disease epithelium.
Am J Respir Crit Care Med
; 187(12): 1374-81, 2013 Jun 15.
Article
em En
| MEDLINE
| ID: mdl-23593951
ABSTRACT
RATIONALE Pulmonary nontuberculous mycobacterial (PNTM) disease has increased over the past several decades, especially in older women. Despite extensive investigation, no consistent immunological abnormalities have been found. Using evidence from diseases such as cystic fibrosis and primary ciliary dyskinesia, in which mucociliary dysfunction predisposes subjects to high rates of nontuberculous mycobacterial disease that increase with age, we investigated correlates of mucociliary function in subjects with PNTM infections and healthy control subjects. OBJECTIVES:
To define ex vivo characteristics of PNTM disease.METHODS:
From 2009 to 2012, 58 subjects with PNTM infections and 40 control subjects were recruited. Nasal nitric oxide (nNO) was determined at the time of respiratory epithelial collection. Ciliary beat frequency at rest and in response to Toll-like receptor (TLR) and other agonists was determined using high-speed video microscopy. MEASUREMENTS AND MAINRESULTS:
We found decreased nNO production, abnormally low resting ciliary beat frequency, and abnormal responses to agonists of TLR2, -3, -5, -7/8, and -9 in subjects with PNTM compared with healthy control subjects. The low ciliary beat frequency in subjects with PNTM was normalized ex vivo by augmentation of the NO-cyclic guanosine monophosphate pathway without normalization of their TLR agonist responses.CONCLUSIONS:
Impaired nNO, ciliary beat frequency, and TLR responses in PNTM disease epithelium identify possible underlying susceptibility mechanisms as well as possible avenues for directed investigation and therapy.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Mucosa Respiratória
/
Receptores Toll-Like
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Pneumopatias
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Infecções por Mycobacterium não Tuberculosas
/
Óxido Nítrico
Tipo de estudo:
Prognostic_studies
Limite:
Adult
/
Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Am J Respir Crit Care Med
Assunto da revista:
TERAPIA INTENSIVA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos