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. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.