PF-4/CXCL4 and CXCL4L1 exhibit distinct subcellular localization and a differentially regulated mechanism of secretion

• Published in: Blood Vol. 109; no. 10; pp. 4127 - 4134
• Main Authors: Lasagni, Laura, Grepin, Renaud, Mazzinghi, Benedetta, Lazzeri, Elena, Meini, Claudia, Sagrinati, Costanza, Liotta, Francesco, Frosali, Francesca, Ronconi, Elisa, Alain-Courtois, Nathalie, Ballerini, Lara, Netti, Giuseppe Stefano, Maggi, Enrico, Annunziato, Francesco, Serio, Mario, Romagnani, Sergio, Bikfalvi, Andreas, Romagnani, Paola
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.05.2007; The Americain Society of Hematology
• Subjects: Biological and medical sciences; Cells, Cultured; Gene Expression Regulation; Hematologic and hematopoietic diseases; Humans; Medical sciences; Platelet Factor 4 - genetics; Platelet Factor 4 - metabolism; RNA, Messenger - metabolism; Signal Transduction - genetics; T-Lymphocytes - metabolism; Tissue Distribution; Transfection; Chemokine; Hematology; Localization; Secretion; Mechanism
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2006-10-052035

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.