An increased number of activated platelets and platelet-leukocyte aggregates are found in patients with chronic inflammatory diseases. Activated platelets can activate the complement system. We have recently determined that properdin, a positive regulator of the alternative pathway that is produced mainly by stimulated leukocytes, promotes complement activation on activated, but not resting, platelets. Unfractionated properdin (that has non-physiological aggregates) induces formation of platelet-leukocyte aggregates. However, the roles that physiological dimers, trimers, and tetramers of properdin play, as well as the molecular mechanisms by which the alternative pathway is involved in this phenomena remain unknown. Here, we have determined that (a) activated platelets, as well as neutrophils, bind physiological forms of properdin and neutrophil-derived properdin; (b) properdin mediates a novel mechanism for alternative pathway activation on activated platelets; and (c) physiological properdin leads to increased platelet-leukocyte aggregate formation in thrombin receptor-stimulated whole blood. The effects of shear stress in properdin-induced aggregate formation and differences between leukocyte subpopulations in platelet-leukocyte aggregate formation have also been assessed. Our data support a role for properdin in cellular microenvironments, contributing to complement activation and aggregate formation, with potential consequences in inflammation pathophysiology.
- Copyright © 2013 by The American Association of Immunologists, Inc.