ASSOCIATION OF SMOOTH-MUSCLE CELL TISSUE FACTOR WITH CAVEOLAE

There is still no satisfactory explanation for the low catalytic activ ity of tissue factor (TF)/factor VII(a) complexes towards coagulation factor X, as found on the apical surface side of cell layers. It has b een hypothesized that TF exists in a latent form. Layers of cultured h uman smooth muscle cells, constitutively expressing TF, were immunogol d-labeled for TF in situ and processed for electron microscopy. We sho wed that, besides internalization and accumulation in lysosomal-like s tructures, TF remained associated with noncoated, flask-shaped microin vaginations of the plasma membrane. These invaginations were identifie d as caveolae. In regions in which intercellular contacts were interru pted, more TF-positive caveolae were observed. Enzymatically detached smooth muscle cells exhibited a similar enlargement of caveolar struct ures. Concomitantly, an increase of catalytic activity of apically for med TF/VIIa complexes towards factor X was found on the suspended cell s. We speculate that caveolae-associated TF may function as a latent p ool of procoagulant activity, which can rapidly be activated at sites in which vessel wall integrity is lost. (C) 1996 by The American Socie ty of Hematology.