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Blood, 15 May 2007, Vol. 109, No. 10, pp. 4127-4134. Prepublished online as a Blood First Edition Paper on January 11, 2007; DOI 10.1182/blood-2006-10-052035. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-10-052035v1 109/10/4127    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 Lasagni, L. Articles by Romagnani, P. Search for Related Content PubMed PubMed Citation Articles by Lasagni, L. Articles by Romagnani, P. Related Collections Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CHEMOKINES, CYTOKINES, AND INTERLEUKINS PF-4/CXCL4 and CXCL4L1 exhibit distinct subcellular localization and a differentially regulated mechanism of secretion Laura Lasagni1, Renaud Grepin2,3, Benedetta Mazzinghi1, Elena Lazzeri1, Claudia Meini1, Costanza Sagrinati1, Francesco Liotta1, Francesca Frosali1, Elisa Ronconi1, Nathalie Alain-Courtois2,3, Lara Ballerini1, Giuseppe Stefano Netti3, Enrico Maggi1, Francesco Annunziato1, Mario Serio1, Sergio Romagnani1, Andreas Bikfalvi2,3, and Paola Romagnani1 1 Excellence Center for Research, Transfer and High Education De Novo Therapies (DENOthe), University of Florence, Florence, Italy; 2 Institut National de la Santé et de la Recherche Médicale (INSERM) E0113, Talence, France; 3 University Bordeaux 1, Talence, France PF-4/CXCL4 is a member of the CXC chemokine family, which is mainly produced by platelets and known for its pleiotropic biological functions. Recently, the proteic product of a nonallelic variant gene of CXCL4 was isolated from human platelets and named as CXCL4L1. CXCL4L1 shows only 4.3% amino acid divergence in the mature protein, but exhibits a 38% amino acid divergence in the signal peptide region. We hypothesized that this may imply a difference in the cell type in which CXCL4L1 is expressed or a difference in its mode of secretion. In different types of transfected cells, CXCL4 and CXCL4L1 exhibited a distinct subcellular localization and a differential regulation of secretion, CXCL4 being stored in secretory granules and released in response to protein kinase C activation, whereas CXCL4L1 was continuously synthesized and secreted through a constitutive pathway. A protein kinase C-regulated CXCL4 secretion was observed also in lymphocytes, a cell type expressing mainly CXCL4 mRNA, whereas smooth muscle cells, which preferentially expressed CXCL4L1, exhibited a constitutive pathway of secretion. These results demonstrate that CXCL4 and CXCL4L1 exhibit a distinct subcellular localization and are secreted in a differentially regulated manner, suggesting distinct roles in inflammatory or homeostatic processes. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: X. Houard, Z. Touat, V. Ollivier, L. Louedec, M. Philippe, U. Sebbag, O. Meilhac, P. Rossignol, and J.-B. Michel Mediators of neutrophil recruitment in human abdominal aortic aneurysms Cardiovasc Res, June 1, 2009; 82(3): 532 - 541. [Abstract] [Full Text] [PDF] A. Zernecke, E. Shagdarsuren, and C. Weber Chemokines in Atherosclerosis: An Update Arterioscler Thromb Vasc Biol, November 1, 2008; 28(11): 1897 - 1908. [Abstract] [Full Text] [PDF] Z. Xiao, G. P. Visentin, K. M. Dayananda, and S. Neelamegham Immune complexes formed following the binding of anti-platelet factor 4 (CXCL4) antibodies to CXCL4 stimulate human neutrophil activation and cell adhesion Blood, August 15, 2008; 112(4): 1091 - 1100. [Abstract] [Full Text] [PDF] J. Vandercappellen, S. Noppen, H. Verbeke, W. Put, R. Conings, M. Gouwy, E. Schutyser, P. Proost, R. Sciot, K. Geboes, et al. Stimulation of angiostatic platelet factor-4 variant (CXCL4L1/PF-4var) versus inhibition of angiogenic granulocyte chemotactic protein-2 (CXCL6/GCP-2) in normal and tumoral mesenchymal cells J. Leukoc. Biol., December 1, 2007; 82(6): 1519 - 1530. [Abstract] [Full Text] [PDF]

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