PLATELET-DERIVED GROWTH-FACTOR INVIVO - LEVELS, ACTIVITY, AND RATE OF CLEARANCE

  • 1 January 1984
    • journal article
    • research article
    • Vol. 64  (2) , 458-469
Abstract
Platelet-derived growth factor (PDGF) is a potent mitogen for many cultured connective tissue cells. It is present in concentrated form within the platelet .alpha.-granules and is believed to be released during platelet degranulation at sites of vascular injury. A sensitive radioreceptor assay was used humans to measure PDGF levels in whole blood serum from normal humans [17.5 .+-. 3.1 (SD) ng/ml] and baboons (2.7 .+-. 1.2 ng/ml). PDGF was not detected in plasma from either species. Plasma was found to substantially reduce the ability of added purified PDGF to bind to the cell surface PDGF receptor on cultured cells, suggesting that plasma may contain a PDGF-binding protein that would serve to inactivate PDGF released into plasma. Calculations of PDGF concentrations in serum have been corrected for the effects of the binding protein. 125I-PDGF injected i.v. into normal baboons was cleared rapidly from the plasma (t1/2 [half-time] = 2 min). The rapid clearance of 125I-PDGF did not result from iodination damage, as purified unlabeled PDGF was cleared with comparable kinetics. The rapid clearance of purified and iodinated PDGF did not result from changes in PDGF structure during purification or from removal of PDGF-associated proteins during purification, as PDGF present in freeze-thaw lysates of fresh platelets was cleared equally rapidly. Release of PDGF at sites of vascular injury would greatly increase the local concentration of PDGF and that PDGF not localized to the site of injury would be rapidly cleared from the circulation.