Association of smooth muscle cell tissue factor with caveolae.
There is still no satisfactory explanation for the low catalytic activity of tissue factor (TF)/factor VII(a) complexes towards coagulation factor X, as found on the apical surface side of cell layers. It has been hypothesized that TF exists in a latent form. Layers of cultured human smooth muscle cells, constitutively expressing TF, were immunogold-labeled for TF in situ and processed for electron microscopy. We showed that, besides internalization and accumulation in lysosomal-like structures, TF remained associated with noncoated, flask-shaped microinvaginations of the plasma membrane. These invaginations were identified as caveolae. In regions in which intercellular contacts were interrupted, more TF-positive caveolae were observed. Enzymatically detached smooth muscle cells exhibited a similar enlargement of caveolar structures. Concomitantly, an increase of catalytic activity of apically formed TF/VIIa complexes towards factor X was found on the suspended cells. We speculate that caveolae-associated TF may function as a latent pool of procoagulant activity, which can rapidly be activated at sites in which vessel wall integrity is lost.
Mulder
A B
AB
Department of Haematology, University Hospital, University of Groningen, The Netherlands.
Smit
J W
JW
Bom
V J
VJ
Blom
N R
NR
Ruiters
M H
MH
Halie
M R
MR
van der Meer
J
J
D001777:Blood Coagulation; D051242:Caveolin 1; D022461:Caveolins; D002448:Cell Adhesion; D002451:Cell Compartmentation; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D002478:Cells, Cultured; D015942:Factor VIIa / Q000378:metabolism; D015951:Factor Xa / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008854:Microscopy, Electron; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D013925:Thromboplastin / Q000502:physiology*
D051242:Caveolin 1; D022461:Caveolins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D013925:Thromboplastin; D015942:Factor VIIa; D015951:Factor Xa