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Respir Res ; 11: 35, 2010 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-20307269

RESUMO

BACKGROUND: Dendritic cells (DC) linking innate and adaptive immune responses are present in human lungs, but the characterization of different subsets and their role in COPD pathogenesis remain to be elucidated. The aim of this study is to characterize and quantify pulmonary myeloid DC subsets in small airways of current and ex-smokers with or without COPD. METHODS: Myeloid DC were characterized using flowcytometry on single cell suspensions of digested human lung tissue. Immunohistochemical staining for langerin, BDCA-1, CD1a and DC-SIGN was performed on surgical resection specimens from 85 patients. Expression of factors inducing Langerhans-type DC (LDC) differentiation was evaluated by RT-PCR on total lung RNA. RESULTS: Two segregated subsets of tissue resident pulmonary myeloid DC were identified in single cell suspensions by flowcytometry: the langerin+ LDC and the DC-SIGN+ interstitial-type DC (intDC). LDC partially expressed the markers CD1a and BDCA-1, which are also present on their known blood precursors. In contrast, intDC did not express langerin, CD1a or BDCA-1, but were more closely related to monocytes.Quantification of DC in the small airways by immunohistochemistry revealed a higher number of LDC in current smokers without COPD and in COPD patients compared to never smokers and ex-smokers without COPD. Importantly, there was no difference in the number of LDC between current and ex-smoking COPD patients.In contrast, the number of intDC did not differ between study groups. Interestingly, the number of BDCA-1+ DC was significantly lower in COPD patients compared to never smokers and further decreased with the severity of the disease. In addition, the accumulation of LDC in the small airways significantly correlated with the expression of the LDC inducing differentiation factor activin-A. CONCLUSIONS: Myeloid DC differentiation is altered in small airways of current smokers and COPD patients resulting in a selective accumulation of the LDC subset which correlates with the pulmonary expression of the LDC-inducing differentiation factor activin-A. This study identified the LDC subset as an interesting focus for future research in COPD pathogenesis.


Assuntos
Células de Langerhans/imunologia , Pulmão/imunologia , Doença Pulmonar Obstrutiva Crônica/imunologia , Fumar/imunologia , Ativinas/genética , Idoso , Antígenos CD/análise , Antígenos CD1/análise , Antígenos de Superfície/análise , Moléculas de Adesão Celular/análise , Diferenciação Celular , Feminino , Citometria de Fluxo , Glicoproteínas , Humanos , Imuno-Histoquímica , Interleucina-15/genética , Peptídeos e Proteínas de Sinalização Intracelular , Lectinas Tipo C/análise , Modelos Lineares , Pulmão/fisiopatologia , Masculino , Lectinas de Ligação a Manose/análise , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Ligante RANK/genética , RNA Mensageiro/análise , Receptores de Superfície Celular/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fumar/efeitos adversos , Fumar/genética , Abandono do Hábito de Fumar
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