Clusterin (13. Blood Cells)

Peripheral blood cells were assayed for clusterin expression. The protein was predominantly detectable in human platelets by immune cytochemistry. The content of clusterin was determined and amounts to 2.5 +/- 1.3 microgram­s/10(9) platelets, thus representing about 2% of the blood pool. Clusterin purified from human platelets had the same molecular weight as plasma clusterin under nonreducing conditions and was composed of two disulfide-linked nonidentical subunits of the same size. Both preparations were sensitive to reduction yielding the two subunits of 35 Kd. In contrast to plasma clusterin, the platelet form was not complexed to apolipoprotein A-I. By immunogold labeling, alpha-granule localization of clusterin was observed. Complete release of platelet clusterin occurred at optimal doses of A23187, phorbol myristate acetate (PMA), and thrombin. Because clusterin mRNA was detected by hybridization in situ in bone marrow-derived megakaryocytes, platelet clusterin is most likely produced and packaged into alpha-granules during megakaryocyte development ^Ref .

Atheromatous plaque development involves platelet aggregation and activation, and abundant clusterin protein was found in advanced human atheromatous lesions. Thus, platelet sequestration and activation may lead to the rapid deployment of clusterin into sites of vascular injury. It is hypothesized that platelet-derived clusterin participates in both shortterm wound repair processes and chronic pathogenic processes at vascular interfaces ^Ref .