Abstract 1129

A close homologue to protein disulfide isomerase (PDI) called ERp57 forms disulfide bonds in glycoproteins in the endoplasmic reticulum and is expressed on the platelet surface. We generated two rabbit antibodies to ERp57. One antibody strongly inhibited ERp57 in a functional assay and strongly inhibited platelet aggregation. There was minimal cross reactivity of this antibody with PDI by Western blot or in the functional assay. Using flow cytometry this antibody substantially inhibited activation of the alphaIIbbeta3 fibrinogen receptor. Furthermore, adding ERp57 to platelets potentiated aggregation. In contrast, adding a catalytically inactive ERp57 inhibited platelet aggregation. When the inactive ERp57 was infused into mice the tail bleeding time was prolonged. We generated two IgG2a monoclonal antibodies that reacted with ERp57 by immunoblot. One of these antibodies inhibited both ERp57 activity and platelet aggregation. The other antibody did not inhibit ERp57 activity or platelet aggregation. When the antibodies were infused into mice the tail bleeding time was prolonged by the inhibitory antibody, but not by the non-inhibitory antibody. Finally, we found that a commonly used monoclonal antibody to PDI also inhibited ERp57 activity. We conclude that a glycoprotein specific member of the PDI family, ERp57, is required for platelet aggregation and hemostasis.


No relevant conflicts of interest to declare.

Author notes


Asterisk with author names denotes non-ASH members.