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Blood, 1 February 2005, Vol. 105, No. 3, pp. 924-930. Prepublished online as a Blood First Edition Paper on September 30, 2004; DOI 10.1182/blood-2004-06-2475. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-06-2475v1 105/3/924    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by von Hundelshausen, P. Articles by Weber, C. Search for Related Content PubMed PubMed Citation Articles by von Hundelshausen, P. Articles by Weber, C. Related Collections Hemostasis, Thrombosis, and Vascular Biology Phagocytes Cell Adhesion and Motility Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CHEMOKINES Heterophilic interactions of platelet factor 4 and RANTES promote monocyte arrest on endothelium Philipp von Hundelshausen, Rory R. Koenen, Markus Sack, Sebastian F. Mause, Wencke Adriaens, Amanda E. I. Proudfoot, Tilman M. Hackeng, and Christian Weber From the Departments of Molecular Cardiovascular Research and Cardiology, University Hospital Aachen, Aachen, Germany; the Institute for Molecular Biotechnology, University of Technology Aachen, Aachen, Germany; the Department of Biochemistry, Cardiovascular Research Institute Maastricht, University Maastricht, Maastricht, the Netherlands; and Serono Pharmaceutical Research Institute, Geneva, Switzerland. The chemokines platelet factor 4 (PF4) and RANTES (regulated on activation normal T cell expressed and secreted) are secreted by activated platelets and influence multiple cell types and biologic processes. For instance, PF4 inhibits progenitor cell proliferation and angiogenesis, while platelet-derived RANTES is involved in vascular recruitment of monocytes. However, little is known about functional interactions of PF4 and RANTES. Here we show that the presence of PF4 enhanced the arrest of RANTES-stimulated monocytes and monocytic cells on activated endothelial cells under flow conditions, while binding of PF4 to the monocyte surface was increased by RANTES. Both RANTES-triggered arrest and PF4 binding involved monocytic chondroitin sulfate. Ligand blots and surface plasmon resonance revealed a robust heterophilic interaction of PF4 with RANTES but not with RANTES variants defective in higher order oligomerization. The tetrameric mutant E26A bound to the monocyte surface without increasing PF4 binding, and monocyte arrest induced by E26A-RANTES was not enhanced by PF4. Stimulation of monocytes with supernatants of activated platelets triggered arrest involving RANTES and PF4, as shown by inhibition studies. Our results suggest that heterophilic interactions with PF4 require structural motifs important in RANTES oligomerization and amplify RANTES-triggered effects on monocyte adhesion. This may have implications for the modulation of inflammatory recruitment by platelet-derived chemokines. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Wang, W. Zhang, R. Tang, R. P. Hebbel, M. A. Kowalska, C. Zhang, J. D. Marth, M. Fukuda, C. Zhu, and Y. 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