Carcinoembryonic antigen (CEA)-related cell adhesion molecules are co-expressed in the human lung and their expression can be modulated in bronchial epithelial cells by non-typable Haemophilus influenzae, Moraxella catarrhalis, TLR3, and type I and II interferons.
BACKGROUND
The carcinoembryonic antigen (CEA)-related cell adhesion molecules CEACAM1 (BGP, CD66a), CEACAM5 (CEA, CD66e) and CEACAM6 (NCA, CD66c) are expressed in human lung. They play a role in innate and adaptive immunity and are targets for various bacterial and viral adhesins. Two pathogens that colonize the normally sterile lower respiratory tract in patients with chronic obstructive pulmonary disease (COPD) are non-typable Haemophilus influenzae (NTHI) and Moraxella catarrhalis. Both pathogens bind to CEACAMs and elicit a variety of cellular reactions, including bacterial internalization, cell adhesion and apoptosis.


METHODS
To analyze the (co-) expression of CEACAM1, CEACAM5 and CEACAM6 in different lung tissues with respect to COPD, smoking status and granulocyte infiltration, immunohistochemically stained paraffin sections of 19 donors were studied. To address short-term effects of cigarette smoke and acute inflammation, transcriptional regulation of CEACAM5, CEACAM6 and different CEACAM1 isoforms by cigarette smoke extract, interferons, Toll-like receptor agonists, and bacteria was tested in normal human bronchial epithelial (NHBE) cells by quantitative PCR. Corresponding CEACAM protein levels were determined by flow cytometry.


RESULTS
Immunohistochemical analysis of lung sections showed the most frequent and intense staining for CEACAM1, CEACAM5 and CEACAM6 in bronchial and alveolar epithelium, but revealed no significant differences in connection with COPD, smoking status and granulocyte infiltration. In NHBE cells, mRNA expression of CEACAM1 isoforms CEACAM1-4L, CEACAM1-4S, CEACAM1-3L and CEACAM1-3S were up-regulated by interferons alpha, beta and gamma, as well as the TLR3 agonist polyinosinic:polycytidylic acid (poly I:C). Interferon-gamma also increased CEACAM5 expression. These results were confirmed on protein level by FACS analysis. Importantly, also NTHI and M. catarrhalis increased CEACAM1 mRNA levels. This effect was independent of the ability to bind to CEACAM1. The expression of CEACAM6 was not affected by any treatment or bacterial infection.


CONCLUSIONS
While we did not find a direct correlation between CEACAM1 expression and COPD, the COPD-associated bacteria NTHi and M. catarrhalis were able to increase the expression of their own receptor on host cells. Further, the data suggest a role for CEACAM1 and CEACAM5 in the phenomenon of increased host susceptibility to bacterial infection upon viral challenge in the human respiratory tract.
Septomics, Research Centre of the Friedrich-Schiller-University Jena, the Jena University Hospital and the Leibniz-Institute for Natural Products Research and Infection Biology - Hans Knöll Institute, Albert-Einstein-Strasse 10, 07745 Jena, Germany.
Esther
E
Klaile
Tilman E
TE
Klassert
Inka
I
Scheffrahn
Mario M
MM
Müller
Annina
A
Heinrich
Kerstin A
KA
Heyl
Hendrik
H
Dienemann
Christiane
C
Grünewald
Robert
R
Bals
Bernhard B
BB
Singer
Hortense
H
Slevogt
D002272:Carcinoembryonic Antigen / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology; D005786:Gene Expression Regulation / Q000276:immunology; D006193:Haemophilus influenzae / Q000276:immunology*; D006801:Humans; D007370:Interferon Type I / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D008168:Lung; D001936:Moraxella catarrhalis / Q000276:immunology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology* / Q000382:microbiology*; D051196:Toll-Like Receptor 3 / Q000276:immunology
D002272:Carcinoembryonic Antigen; D015815:Cell Adhesion Molecules; D016207:Cytokines; D007370:Interferon Type I; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D007371:Interferon-gamma