EFFECT OF CIGARETTE-SMOKE ON THE MESSENGER-RNA AND PROTEIN EXPRESSIONOF CARCINOEMBRYONIC ANTIGEN (CEA), A POSSIBLE CHEMOATTRACTANT FOR NEUTROPHILS IN HUMAN BRONCHIOLOALVEOLAR TISSUES

Background - The concentration of carcinoembryonic antigen (CEA), know n as a marker of malignant transformation and chronic inflammation, is increased in bronchoalveolar lavage fluid obtained from smokers compa red with fluid from non-smokers. This study investigated the mechanism and biological significance of CEA production in the lungs of smokers by evaluating protein and mRNA expression in non-carcinomatous lung p arenchymal tissues and in cell lines derived from human fetal lung. Me thods - Lung parenchymal tissue free from cancer or an inflammatory le sion was obtained from five non-smokers (four with lung cancer, one wi th pulmonary mycetoma), five ex-smokers (all with lung cancer except f or one with mesothelioma), and 14 smokers (nine with lung cancer, five with emphysema) at surgery or necropsy. Cancer tissue was also collec ted simultaneously from the subjects with lung cancer. CEA protein in the tissue homogenates was measured by enzyme linked immunoassay. CEA mRNA expression in the non-carcinomatous parenchymal tissue and cancer tissue was evaluated by in situ hybridisation using CEA specific ribo probe and was semiquantitated by counting the number of silver grains per cell, CEA mRNA expression was also compared in three cell lines de rived from human fetal lung (IMR-90, MRC-9, and CCD-14Br) after in vit ro stimulation with medium exposed to cigarette smoke or air. Chemoatt ractant activity of purified CEA for neutrophils and monocytes was als o studied in vitro. Results - CEA content in non-carcinomatous lung ti ssue was increased in smokers with emphysema (mean (SD) 38.0 (9.2) ng/ mg protein) or with lung cancer (38.2 (21.6)) compared with non-smoker s (11.0 (5.4)) or ex-smokers (5.9 (2.2)). CEA mRNA expression in non-c arcinomatous tissue, expressed by average number of grains per cell, w as also increased in smokers with emphysema (mean (SD) 11.2 (4.1)) or with lung cancer (14.0 (8.4)) compared with non-smokers (3.1 (0.6)) or ex-smokers (4.0 (1.7) CEA content in carcinomatous tissues was 42.8 ( 37.3) for non-smokers, 38.2 (42.4)) for ex-smokers, and 59.0 (22.5) fo r smokers. The CEA content in carcinomatous tissue was higher than in non-carcinomatous tissue, but there was no difference between non-smok ers, ex-smokers, and smokers. The numbers of grains per cell in carcin omatous tissue were higher than in non-carcinomatous tissues, but not different among non-smokers (30.3 (3.9)), ex-smokers (38.3 (13.8)), an d smokers (44.3 (5.2)). CEA mRNA expression in the cell lines was upre gulated after the incubation with smoke-treated medium. Purified CEA w as chemoattractant for neutrophils but not for monocytes in vitro. Con clusions - mRNA and protein expression of CEA were increased in the no rmal lung tissue from smokers compared with non-smokers or ex-smokers. Since CEA content and mRNA expression were no different between smoke rs with non-small cell lung cancer and those with non-carcinomatous di sease, it is unlikely that CEA expression in non-carcinomatous lung pa renchymal tissue was influenced by the presence of the tumour and is c onsistent with the effect of smoking. This is supported by in vitro st udies which show that cigarette smoke could induce CEA mRNA expression in fetal lung derived cells. In addition, CEA might play a part in re cruitment of neutrophils into the lower respiratory tract.