Ligand-regulated secretion of recombinant annexin V from cultured thyroid epithelial cells

The exposure of anionic phospholipidson the external surface of injured endothelial cells and activatedplatelets is a primary biological signal to initiate blood coagulation.Disease conditions that promote the formation of ectopic thrombi resultin tissue ischemia. Annexins, Ca²⁺-dependentanionic phospholipid binding proteins, are potential therapeutic agentsfor the inhibition of coagulation. We have designed a transgene thattargets secretion of annexin V from cultured thyroid cells under thecontrol of doxycycline. Our results indicate that annexin V in theendoplasmic reticulum (ER)/Golgi lumen does not affect the synthesis,processing, and secretion of thyroglobulin. ER luminal Ca²⁺was moderately increased and can be released by inositol1,4,5-trisphosphate. Our study demonstrates that targeting andsecretion of annexin V through the secretory pathway of mammalian cellsdoes not adversely affect cellular function. Regulated synthesis andrelease of annexin V may exert anticoagulatory and anti-inflammatoryeffects systemically and may prove useful in further developingtherapeutic strategies for conditions including antiphospholipid syndrome.