Store-mediated calcium entry in the regulation of phosphatidylserine exposure in blood cells from Scott patients

Summary

Scott syndrome is a bleeding disorder, characterized by impaired surface exposure of procoagulant phosphatidylserine (PS) on platelets and other blood cells, following activation with Ca²⁺-elevating agents. Since store-mediated Ca²⁺ entry (SMCE) forms an important part of the Ca²⁺ response in various blood cells, it has been proposed that deficiencies in Ca²⁺ entry may relate to the impaired PS exposure in the Scott syndrome. Here, we have tested this hypothesis by investigating the relationship between Ca²⁺ fluxes and PS exposure in platelets as well as B-lymphoblasts derived from the original Scott patient (M.S.), a newly identified Welsh patient (V.W.) with similar bleeding symptoms, and two control subjects. Procoagulant activity of V.W. platelets in suspension, measured after stimulation with collagen/thrombin or Ca²⁺-ionophore, ionomycin, resulted in 52% or 17%, respectively, compared to that of correspondingly activated control platelets. Procoagulant activity of V.W. erythrocytes treated with Ca²⁺-ionophore resulted in less than 6% of the activity of control erythrocytes. Single-cell Ca²⁺ responses of M.S. and V.W. platelets, adhering to collagen, were similar to those of platelets from control subjects, while PS exposure was reduced to 7% and 15%, respectively, compared to controls. Stimulation of non-apoptotic B-lymphoblasts derived from both patients and controls with Ca²⁺-ionophore or agents causing Ca²⁺ mobilization and SMCE, resulted in similar Ca²⁺ responses. However, in lymphoblasts from M.S. and V.W. Ca²⁺-induced PS exposure was reduced to 7% and 13% of the control lymphoblasts, respectively. We conclude that i. patient V.W. is a new case of Scott syndrome, ii. Ca²⁺ entry in the platelets and lymphoblasts from both Scott patients is normal, and iii. elevated [Ca²⁺]_i as caused by SMCE is not sufficient to trigger PS exposure.

Keywords

Procoagulant activity - Scott syndrome - platelets - B-lymphoblasts - intracellular calcium

• References

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