Endothelial cell adhesion molecule CD146: implications for its role in the pathogenesis of COPD.
CD146 is an adhesion molecule localized at endothelial cell junctions and facilitates cell-cell interactions. The circulating soluble form (sCD146) lacks both the intracellular and the transmembrane domains. In this study we show that CD146 expression was significantly decreased in the lung tissue of smokers with chronic obstructive pulmonary disease (COPD) and also in rats exposed to second-hand smoke (SHS). Concurrently, levels of sCD146 were increased in both the plasma and bronchoalveolar lavage fluid (BALF) of COPD patients as well as in BALF from rats exposed to SHS. Decreased or abolished CD146 protein expression in rat pulmonary micro- and macrovascular endothelial cells was found after treatment with cigarette smoke extract (CSE), proinflammatory cytokine interleukin 18 (IL-18) or after silencing CD146 expression with siRNA. The decrease in CD146 protein was accompanied by increased endothelial monolayer permeability and enhanced macrophage infiltration in vitro. In CD146 knockout (KO) mice, distinct perivascular oedema was seen and increased numbers of inflammatory cells, along with increased protein levels in BALF. Increased sCD146 was found in BALF and plasma from patients with COPD. The circulating plasma levels of sCD146 correlated positively with the presence of anti-endothelial cell antibodies (AECAs). sCD146 in combination with AECAs may be useful markers for early detection of COPD. Our study indicates that loss of CD146 function damages pulmonary endothelial integrity. This damage may represent part of the pathophysiological processes that are involved in the basic aetiology of COPD/emphysema.
['Kratzer|Adelheid|A|', 'Chu|Hong Wei|HW|', 'Salys|Jonas|J|', 'Moumen|Zakaria|Z|', 'Leberl|Maike|M|', 'Bowler|Russ|R|', 'Cool|Carlyne|C|', 'Zamora|Martin|M|', 'Taraseviciene-Stewart|Laima|L|']
D000368:Aged D000818:Animals D001323:Autoantibodies D015415:Biomarkers D001992:Bronchoalveolar Lavage Fluid D051929:CD146 Antigen D002199:Capillary Permeability D016022:Case-Control Studies D002478:Cells, Cultured D004195:Disease Models, Animal D042241:Early Diagnosis D042783:Endothelial Cells D005260:Female D005786:Gene Expression Regulation D006801:Humans D020382:Interleukin-18 D008168:Lung D008264:Macrophages D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D018345:Mice, Knockout D008875:Middle Aged D011237:Predictive Value of Tests D029424:Pulmonary Disease, Chronic Obstructive D011654:Pulmonary Edema D011656:Pulmonary Emphysema D034622:RNA Interference D051381:Rats D017207:Rats, Sprague-Dawley D014028:Tobacco Smoke Pollution D014162:Transfection
endothelial cells cell adhesion emphysema inflammation vascular integrity