The UspA1 protein of Moraxella catarrhalis induces CEACAM-1-dependent apoptosis in alveolar epithelial cells.
Moraxella catarrhalis is a major cause of exacerbations of chronic obstructive pulmonary disease (COPD) and emphysema. M. catarrhalis-specific UspA1 and the epithelial carcinoembryonic antigen-related cell adhesion molecule (CEACAM1) were required to induce apoptosis. M. catarrhalis-induced apoptosis was significantly enhanced in HeLa cells stably transfected with CEACAM1, compared with HeLa cells not expressing CEACAM1. Infected cells showed increased activity of caspases 3, 6, and 9 but not of caspase 8. Reduced expression of Bcl-2, translocation of Bax into the mitochondria, and cytosolic increase of apoptosis-inducing factor in M. catarrhalis-infected cells implicated the involvement of mitochondrial death pathways. In conclusion, M. catarrhalis induced apoptosis in pulmonary epithelial cells--a process that was triggered by interaction between CEACAM1 and UspA1. Thus, M. catarrhalis-induced apoptosis of pulmonary epithelial cells may contribute to the development of COPD and emphysema.
N'Guessan
Philippe Dje
PD
Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charite-Universitatsmedizin Berlin, Berlin, Germany.
Vigelahn
Manuel
M
Bachmann
Sebastian
S
Zabel
Solveig
S
Opitz
Bastian
B
Schmeck
Bernd
B
Hippenstiel
Stefan
S
Zweigner
Janine
J
Riesbeck
Kristian
K
Singer
Bernhard B
BB
Suttorp
Norbert
N
Slevogt
Hortense
H
D015703:Antigens, CD / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology*; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D004847:Epithelial Cells / Q000382:microbiology*; D006367:HeLa Cells; D006801:Humans; D001936:Moraxella catarrhalis / Q000378:metabolism / Q000472:pathogenicity*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000382:microbiology*
D015703:Antigens, CD; D001425:Bacterial Outer Membrane Proteins; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; C089675:UspA protein, Moraxella catarrhalis