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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.
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Submitted October 18, 2006
Accepted January 5, 2007
PF-4/CXCL4 and CXCL4L1 exhibit distinct subcellular localization and a differentially regulated mechanism of
secretion
Laura Lasagni, Renaud Grepin, Benedetta Mazzinghi, Elena Lazzeri, Claudia Meini, Costanza Sagrinati, Francesco Liotta, Francesca Frosali, Elisa Ronconi, Nathalie Alain-Courtois, Lara Ballerini, Giuseppe Stefano Netti, Enrico Maggi, Francesco Annunziato, Mario Serio, Sergio Romagnani, Andreas Bikfalvi, and Paola Romagnani*
Excellence Center for Research, Transfer and High Education, DENOthe, University of Florence, Florence, Italy
INSERM E113 "Molecular Angiogenesis Laboratory, Universite Bordeaux I, Bordeaux, France
Department of Biomedical Science, University of Foggia, Foggia, Italy
* Corresponding author; email: p.romagnani{at}dfc.unifi.it.
PF-4/CXCL4 is a member of the CXC chemokine family, which is mainly produced by platelets and known for its pleiotropic biologic 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, while 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.

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