Abstract
Zirc(II) accumulated by platelets has profound effects on platelet activity. This study is focused on the distribution of Zn(II) between human platelet subcellular compartments. After incubation with ^86^Rb^+^ and platelet lysis, the organelles were separated by sucrose density gradient centrifugation. Fibrinogen served as a marker for α‐granules. ^86^Rb^+^ and factor XIII served as markers for the cytoplasmic fractions. Zn(II) was found to be distributed between the cytoplasm and the α‐granules, with variations between different individual units. The total platelet Zn concentration and its relative subcellular distribution were dependent on its extracellular level. Incubation of platelets with 100 μM Zn(II) resulted in a twofold increase of its level in the cytoplasm and by one order of magnitude in the α‐granules. In addition to the anticipated factor XIII activity in the cytoplasmic pool fraction, we found thrombin‐inducible factor XIII activity within the α‐granules. Immunoblotting confirmed the presence of both the a and b subunits of plasma factor XIII (a~2~b~2~ form) in the α‐granules. As fibrinogen is not synthesized in the platelet, we propose that by virtue of their mutual binding, fibrinogen, Zn(II) and plasma factor XIII‐a~2~b~2~ are simultaneously taken up into the α‐granules by endocytosis, presumably through the vehicle of the GPIIb/IIIa fibrinogen receptor. A rationale for copackaging these components within the α‐granules is that Zn(II) inhibits factor XIII activity and thereby prevents the premature cross‐linking of the concentrated fibrinogen prior to platelet activation and secretion. By contrast, cytoplasmic Zn(II) may increase platelet responsiveness to agonists due to its interaction with cytoplasmic modulators of platelet activity. © 1993 Wiley‐Liss, Inc.