Interactions of Platelet Factor 4 with the Vessel Wall

Bruce S. Sachais; Abd Al-Roof Higazi; Douglas B. Cines; Mortimer Poncz; M. Anna Kowalska

doi:10.1055/s-2004-831048

Seminars in Thrombosis and Hemostasis, Inhaltsverzeichnis

Semin Thromb Hemost 2004; 30(3): 351-358
DOI: 10.1055/s-2004-831048

Interactions of Platelet Factor 4 with the Vessel Wall

Bruce S. Sachais¹ , Abd Al-Roof Higazi¹ , Douglas B. Cines¹ , Mortimer Poncz¹ ^, ² , M. Anna Kowalska² ^, ³

¹Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
²Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
³Assistant Professor, Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania

Abstract

Platelet factor 4 (PF4) is a platelet-specific protein that is stored in platelet α granules and released following platelet activation. PF4 was the first chemokine that was isolated, but unlike other chemokines, it may not have a clear role in inflammation. Gathering evidence suggests that unlike other chemokines that bind to specific receptors, PF4’s biology depends on its unusually high affinity for heparan sulfates and other negatively charged molecules at concentrations attained in the immediate vicinity of activated platelets. There has been one report that PF4 binds to CXCR3B, a chemokine receptor isoform that may be present in some vascular beds, but the biological relevance of this single observation is not clear. We propose that the main biological role of PF4 and the basis for its presence in the α granules of all known mammalian platelets is to neutralize surface heparan sulfate side-chains of glycosaminoglycans and to optimize thrombus development at sites of vascular injury. In addition, the binding of PF4 to surface glycosaminoglycans may also underlie its angiostatic and proatherogenic properties. Additionally, PF4 binds to several other proteins that are central to thrombosis, angiogenesis, and atherogenesis. These interactions may also contribute to its biological and pathobiological effects. Certainly, future studies using in vivo models to test biological relevance of each of these proposed mechanisms by which PF4 interacts with the vasculature are needed, as are studies to define the importance of PF4 binding to CXCR3B.

KEYWORDS

Platelet factor 4 - PF4 - thrombosis - angiogenesis - atherosclerosis - chemokine - heparin

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M. Anna KowalskaPh.D.

Children’s Hospital of Philadelphia, 3516 Civic Center Blvd, ARC

Rm. 316I, Philadelphia, PA 19104

eMail: kowalska@email.chop.edu