PMID- 19729666 OWN - NLM STAT- MEDLINE DCOM- 20100104 LR - 20211020 IS - 1535-4970 (Electronic) IS - 1073-449X (Print) IS - 1073-449X (Linking) VI - 180 IP - 12 DP - 2009 Dec 15 TI - Lung dendritic cell expression of maturation molecules increases with worsening chronic obstructive pulmonary disease. PG - 1179-88 LID - 10.1164/rccm.200904-0552OC [doi] AB - RATIONALE: Dendritic cells (DCs) have not been well studied in chronic obstructive pulmonary disease (COPD), yet their integral role in activating and differentiating T cells makes them potential participants in COPD pathogenesis. OBJECTIVES: To determine the expression of maturation molecules by individual DC subsets in relationship to COPD stage and to expression of the acute activation marker CD69 by lung CD4(+) T cells. METHODS: We nonenzymatically released lung leukocytes from human surgical specimens (n = 42) and used flow cytometry to identify three DC subsets (mDC1, mDC2, and pDC) and to measure their expression of three costimulatory molecules (CD40, CD80 and CD86) and of CD83, the definitive marker of DC maturation. Spearman nonparametric correlation analysis was used to identify significant correlations between expression of DC maturation molecules and COPD severity. MEASUREMENTS AND MAIN RESULTS: Expression of CD40 by mDC1 and mDC2 and of CD86 by mDC2 was high regardless of GOLD stage, but CD80 and CD83 on these two DC subsets increased with disease progression. pDC also showed significant increases in expression of CD40 and CD80. Expression of all but one of the DC molecules that increased with COPD severity also correlated with CD69 expression on lung CD4(+) T cells from the same patients, with the exception of CD83 on mDC2. CONCLUSIONS: This cross-sectional study implies that COPD progression is associated with significant increases in costimulatory molecule expression by multiple lung DC subsets. Interactions with lung DCs may contribute to the immunophenotype of CD4(+) T cells in advanced COPD. Clinical trial registered with www.clinicaltrials.gov (NCT00281229). FAU - Freeman, Christine M AU - Freeman CM AD - Pulmonary and Critical Care Medicine Section, VA Ann Arbor Healthcare System, Ann Arbor, MI, USA. FAU - Martinez, Fernando J AU - Martinez FJ FAU - Han, MeiLan K AU - Han MK FAU - Ames, Theresa M AU - Ames TM FAU - Chensue, Stephen W AU - Chensue SW FAU - Todt, Jill C AU - Todt JC FAU - Arenberg, Douglas A AU - Arenberg DA FAU - Meldrum, Catherine A AU - Meldrum CA FAU - Getty, Christi AU - Getty C FAU - McCloskey, Lisa AU - McCloskey L FAU - Curtis, Jeffrey L AU - Curtis JL LA - eng SI - ClinicalTrials.gov/NCT00281229 GR - R01 CA094121-05/CA/NCI NIH HHS/United States GR - P30 CA46952/CA/NCI NIH HHS/United States GR - K24HL04212/HL/NHLBI NIH HHS/United States GR - R01 CA094121/CA/NCI NIH HHS/United States GR - R01 HL082480/HL/NHLBI NIH HHS/United States GR - KL2 RR024987/RR/NCRR NIH HHS/United States GR - K24 HL004212/HL/NHLBI NIH HHS/United States GR - N01 HR046162/HR/NHLBI NIH HHS/United States GR - T32 HL07749/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20090903 PL - United States TA - Am J Respir Crit Care Med JT - American journal of respiratory and critical care medicine JID - 9421642 RN - 0 (Antigens, CD) RN - 0 (Antigens, Differentiation, T-Lymphocyte) RN - 0 (CD69 antigen) RN - 0 (Lectins, C-Type) SB - IM CIN - Am J Respir Crit Care Med. 2009 Dec 15;180(12):1166-7. PMID: 19949238 MH - Aged MH - Antigens, CD/immunology MH - Antigens, Differentiation, T-Lymphocyte/immunology MH - CD4-Positive T-Lymphocytes/immunology MH - Cell Culture Techniques MH - Cell Differentiation/immunology MH - Cross-Sectional Studies MH - Dendritic Cells/*immunology MH - Female MH - Flow Cytometry MH - Humans MH - Lectins, C-Type MH - Lung/*immunology MH - Male MH - Middle Aged MH - Pulmonary Disease, Chronic Obstructive/*immunology MH - Severity of Illness Index MH - Smoking/immunology PMC - PMC2796731 EDAT- 2009/09/05 06:00 MHDA- 2010/01/05 06:00 PMCR- 2010/12/15 CRDT- 2009/09/05 06:00 PHST- 2009/09/05 06:00 [entrez] PHST- 2009/09/05 06:00 [pubmed] PHST- 2010/01/05 06:00 [medline] PHST- 2010/12/15 00:00 [pmc-release] AID - 200904-0552OC [pii] AID - ajrccm180121179 [pii] AID - 10.1164/rccm.200904-0552OC [doi] PST - ppublish SO - Am J Respir Crit Care Med. 2009 Dec 15;180(12):1179-88. doi: 10.1164/rccm.200904-0552OC. Epub 2009 Sep 3.