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Fibroblast tissue factor: calcium and ionophore induce shape changes,
release of membrane vesicles, and redistribution of tissue factor antigen
in addition to increased procoagulant activity
SD Carson, GA Perry and SJ Pirruccello
Department of Pathology, University of Nebraska Medical Center, Omaha
68198-6495.
The coagulant activity of tissue factor (TF) in the membranes of cultured
cells is increased after physical disruption of the cells, and a similar
increase can be elicited by treatment of cell cultures with calcium
ionophore and calcium. We observed that the supernatants of cultures
treated with calcium and ionophore 4-Br-A23187 contained more TF activity
than those of control cultures. Phase contrast microscopy showed that
cultures treated with ionophore and calcium contained rounded cells,
membrane vesicles, and cell fragments. Laser-activated fluorescence
microscopy of cells stained for tissue factor antigen showed that
4-Br-A23187, in the presence of 5 mmol/L calcium, caused progressive
changes in cell morphology. Treatment of cultures with thrombin receptor
agonist peptide caused a transient increase in cytoplasmic calcium, but had
no short-term effect on TF activity or cell morphology. These combined
results show that 4-Br-A23187, with extracellular calcium, increases TF
activity concomitant with dramatic changes in cell morphology and the
plasma membrane. The effect of increased cytoplasmic calcium on TF
expression may therefore be similar in mechanism to other models of cell
injury and may be caused by the effects of a sustained increase of
cytosolic calcium on cellular elements that influence membrane stability
and the distribution of TF per se.
Volume 84,
Issue 2,
pp. 526-534,
07/15/1994
Copyright © 1994 by The American Society of Hematology

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