Functional regulation of platelet/endothelial cell adhesion molecule-1 by TGF-beta 1 in promonocytic U-937 cells.
Platelet endothelial cell adhesion molecule-1 (PECAM-1) is a widely distributed cell adhesion molecule present on monocytes, macrophages, and monocytic cell lines. Treatment of the promonocytic cell line U-937 with TGF-beta 1 induces homotypic cellular aggregations, simultaneous with an increase in surface expression and specific transcripts of PECAM-1. The TGF-beta-induced cell adhesion phenomena are not dependent on LFA-1, intercellular adhesion molecule-1 (ICAM-1), very late Ag-4 (VLA-4), or very late Ag-5 (VLA-5). However, the phenomena seem to be directly mediated by PECAM-1 because 1) it is inhibited by the addition of Abs or an antisense oligonucleotide specific for PECAM-1; and 2) TGF-beta 1-treated U-937 cells bind to PECAM-1-expressing mouse transfectant fibroblasts, but not to mock transfectants. In addition, this aggregation phenomena are divalent cation-dependent and requires the integrity of the cytoskeleton. Analysis of the intracellular signaling pathways indicates that TGF-beta 1 induces protein kinase C activity, as well as PECAM-1 phosphorylation and association with cytoskeletal components. Furthermore, in this model, an autocrine mechanism for releasing the bioactive form of TGF-beta 1 operates, allowing PECAM-1 activation. These results provide evidence that TGF-beta 1 regulates PECAM-1 function by increasing the expression and activating the adhesion of PECAM-1 in monocytic cells. These two mechanisms seem to be necessary for adhesion because independent inhibition of either expression or activation of PECAM-1 leads to abrogation of cellular aggregation.
Lastres
P
P
Department of Immunology, Center of Biological Investigations, Madrid, Spain.
Almendro
N
N
Bellón
T
T
López-Guerrero
J A
JA
Eritja
R
R
Bernabéu
C
C
D015214:Antigens, Differentiation, Myelomonocytic / Q000502:physiology*; D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002455:Cell Division; D002460:Cell Line; D003599:Cytoskeleton / Q000502:physiology; D005434:Flow Cytometry; D006801:Humans; D008969:Molecular Sequence Data; D009000:Monocytes / Q000502:physiology*; D010766:Phosphorylation; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011493:Protein Kinase C / Q000378:metabolism; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000502:physiology*
D015214:Antigens, Differentiation, Myelomonocytic; D015815:Cell Adhesion Molecules; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D016212:Transforming Growth Factor beta; D011493:Protein Kinase C