Lena Wehlin1, Magnus Löfdahl, Joachim Lundahl, Magnus Sköld. 1. Division of Clinical Immunology and Allergy, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, L2:04, S-171 76 Stockholm, Sweden. Lena.Wehlin@medks.ki.se
Abstract
RATIONALE AND OBJECTIVES: COPD is characterized by irreversible airflow obstruction. It has, however, become clear that COPD also is a systemic disease. In the present study, we sought to investigate its impact on different peripheral leukocyte subpopulations that are recognized as important effector cells in the lung tissue. METHODS: We enrolled 20 patients with stable, moderate COPD (FEV1, 33 to 69%). Ten asymptomatic smokers and 10 nonsmokers served as control groups. Flow cytometry and whole blood analysis were used to minimize unwanted ex vivo modulation. Oxidative burst and adhesion molecule mobilization were analyzed on freshly drawn cells and after in vitro activation. MEASUREMENTS AND MAIN RESULTS: We found reduced oxidative burst in neutrophils, monocytes, and eosinophils after in vitro stimulation with tumor necrosis factor (TNF) and the bacterial peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP) in both COPD patients and asymptomatic smokers as compared to nonsmoking control subjects. Vascular involvement was determined as increased soluble intercellular adhesion molecule-1 (sICAM-1) in the COPD group. There were no differences in adhesion molecule expression among the three groups. However, in COPD patients who had smoked the same morning prior to blood sampling, we found a reduced ability to mobilize adhesion molecule CD11b after TNF plus fMLP activation in all investigated cell types. "Acute" smoking did not significantly alter respiratory burst measurements. CONCLUSIONS: Both COPD patients and asymptomatic smokers have increased levels of sICAM-1 and a reduced intracellular oxidative burst in vitro, indicating a vascular endothelial activation and a possible state of refractoriness in circulating phagocytes in COPD. Although expression and mobilization of adhesion molecules were similar between groups, the acute smoke effect on CD11b points out the value of information on smoking behavior when analyzing function of peripheral inflammatory cells in a smoking population.
RATIONALE AND OBJECTIVES:COPD is characterized by irreversible airflow obstruction. It has, however, become clear that COPD also is a systemic disease. In the present study, we sought to investigate its impact on different peripheral leukocyte subpopulations that are recognized as important effector cells in the lung tissue. METHODS: We enrolled 20 patients with stable, moderate COPD (FEV1, 33 to 69%). Ten asymptomatic smokers and 10 nonsmokers served as control groups. Flow cytometry and whole blood analysis were used to minimize unwanted ex vivo modulation. Oxidative burst and adhesion molecule mobilization were analyzed on freshly drawn cells and after in vitro activation. MEASUREMENTS AND MAIN RESULTS: We found reduced oxidative burst in neutrophils, monocytes, and eosinophils after in vitro stimulation with tumor necrosis factor (TNF) and the bacterial peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP) in both COPDpatients and asymptomatic smokers as compared to nonsmoking control subjects. Vascular involvement was determined as increased soluble intercellular adhesion molecule-1 (sICAM-1) in the COPD group. There were no differences in adhesion molecule expression among the three groups. However, in COPDpatients who had smoked the same morning prior to blood sampling, we found a reduced ability to mobilize adhesion molecule CD11b after TNF plus fMLP activation in all investigated cell types. "Acute" smoking did not significantly alter respiratory burst measurements. CONCLUSIONS: Both COPDpatients and asymptomatic smokers have increased levels of sICAM-1 and a reduced intracellular oxidative burst in vitro, indicating a vascular endothelial activation and a possible state of refractoriness in circulating phagocytes in COPD. Although expression and mobilization of adhesion molecules were similar between groups, the acute smoke effect on CD11b points out the value of information on smoking behavior when analyzing function of peripheral inflammatory cells in a smoking population.
Authors: Janel R Harting; Angela Gleason; Debra J Romberger; Susanna G Von Essen; Fang Qiu; Neil Alexis; Jill A Poole Journal: J Toxicol Environ Health A Date: 2012
Authors: Patrick Mallia; Simon D Message; Marco Contoli; Katrina K Gray; Aurica Telcian; Vasile Laza-Stanca; Alberto Papi; Luminita A Stanciu; Sarah Elkin; Onn M Kon; Malcolm Johnson; Sebastian L Johnston Journal: Respir Res Date: 2013-07-08