@article {Kratzerp3892, author = {Adelheid Kratzer and Jonas Salys and Hong Wei Chu and Martin Zamora and Laima Taraseviciene-Stewart}, title = {CD146 in the pathogenesis of COPD}, volume = {38}, number = {Suppl 55}, elocation-id = {p3892}, year = {2011}, publisher = {European Respiratory Society}, abstract = {Background: Chronic obstructive lung diseases (COPD) are the major cause of death and disability worldwide. The major risk factor for COPD is tobacco smoke. Cell adhesion molecule CD146 is expressed in all types of human endothelial cells (EC) and exists in a membrane-anchored and a soluble form (sCD146). The plasma concentration of sCD146 is modulated in inflammatory diseases associated with endothelial alterations.Aims and objectives: To investigate the role of endothelial CD146 in the pathogenesis of cigarette smoke (CS)-induced emphysema.Methods: Sprague Dawley rats were exposed to second hand CS for two months. The lung tissue and bronchoalveolar lavage (BAL) cells were examined for CD146 gene and protein expression and emphysema development as measured by MLI. sCD146 levels were determined in circulation and BAL fluid in rats and in patients with COPD. CD146 expression and function was also examined in rat pulmonary EC exposed to CS in vitro.Results: Sprague Dawley rats exposed to cigarette smoke for 2 months developed significant emphysematous changes (as measured by mean linear intercept) and had increased levels of circulating and bronchoalveolar lavage fluid sCD146. Treatment of rat pulmonary EC with cigarette smoke extract in vitro also resulted in a decreased membrane-bound CD146 expression and increased sCD146 levels in the medium. Moreover, circulating levels of sCD146 were significantly increased in serum of patients with COPD and correlated with the disease severity.Conclusion: Our data indicate that CD146 is involved in CS-induced vascular dysfunction and that sCD146 can be a candidate marker for COPD/emphysema.Funded by AHA 0735388N, FAMRI CIA 072053, Emphysema Research Fund and Bixler Family Foundation.}, issn = {0903-1936}, URL = {https://erj.ersjournals.com/content/38/Suppl_55/p3892}, eprint = {https://erj.ersjournals.com/content}, journal = {European Respiratory Journal} }