The nuclear autoantigen CENP-B displays cytokine-like activities toward vascular smooth muscle cells.
OBJECTIVE
A growing number of intracellular autoantigenic polypeptides have been found to play a second biologic role when they are present in the extracellular medium. We undertook this study to determine whether the CENP-B nuclear autoantigen could be added to this set of bifunctional molecules.


METHODS
Purified CENP-B or CENP-B released from apoptotic cells was tested for surface binding to a number of human cell types by cell-based enzyme-linked immunosorbent assay, flow cytometry, and indirect immunofluorescence. The biologic effects of CENP-B on the migration, interleukin secretion, and signaling pathways of its specific target cells were evaluated.


RESULTS
CENP-B was found to bind specifically to the surface of human pulmonary artery smooth muscle cells (SMCs) and not to fibroblasts or endothelial cells (ECs). Furthermore, CENP-B bound preferentially to SMCs of the contractile type rather than to SMCs of the synthetic type. Binding of CENP-B to SMCs stimulated their migration during in vitro wound healing assays, as well as their secretion of interleukins 6 and 8. The mechanism by which CENP-B mediated these effects involved the focal adhesion kinase, Src, ERK-1/2, and p38 MAPK pathways. Finally, CENP-B released from apoptotic ECs was found to bind to SMCs, thus indicating a plausible in vivo source of extracellular CENP-B.


CONCLUSIONS
These novel biologic roles of the nuclear autoantigen CENP-B open up a new perspective for studying the pathogenic role of anti-CENP-B autoantibodies.
Robitaille
Geneviève
G
Notre-Dame Hospital, Centre Hospitalier de l'Université de Montréal, Université de Montréal, Montréal, Québec, Canada.
Hénault
Jill
J
Christin
Marie-Soleil
MS
Senécal
Jean-Luc
JL
Raymond
Yves
Y
D000328:Adult; D017209:Apoptosis; D001324:Autoantigens / Q000276:immunology* / Q000378:metabolism; D002455:Cell Division; D002465:Cell Movement; D002478:Cells, Cultured; D051936:Centromere Protein B / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D000939:Epitopes; D005347:Fibroblasts / Q000166:cytology; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D008168:Lung / Q000166:cytology; D020935:MAP Kinase Signaling System / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000276:immunology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding / Q000276:immunology; D011651:Pulmonary Artery / Q000166:cytology*; D019061:src-Family Kinases / Q000378:metabolism
D001324:Autoantigens; C497926:CENPB protein, human; D051936:Centromere Protein B; D016207:Cytokines; D000939:Epitopes; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019061:src-Family Kinases