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Prepublished online as a Blood First Edition Paper on February 27, 2003; DOI 10.1182/blood-2002-06-1782. This Article Full Text (PDF) All Versions of this Article: 2002-06-1782v1 101/11/4245    most recent Alert me when this article is cited Alert me if a correction is posted 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 Ding, Z. Articles by Waddell, T. K Search for Related Content PubMed PubMed Citation Articles by Ding, Z. Articles by Waddell, T. K Social Bookmarking                   What's this? Submitted June 17, 2002 Accepted December 10, 2002 L-selectin stimulation enhances functional expression of surface CXCR4 in lymphocytes: implications for cellular activation during adhesion and migration Ziqiang Ding, Thomas B Issekutz, Gregory P Downey, and Thomas K Waddell* Division of Thoracic Surgery, Toronto General Hospital, Toronto, ON, Canada Division of Respiratory Medicine, Toronto General Hospital, Toronto, ON, Canada Department of Pediatrics, IWK Grace Health Center, Halifax, NS, Canada * Corresponding author; email: tom.waddell{at}uhn.on.ca. L-selectin mediates leukocyte tethering and rolling, the first step in a sequential process of leukocyte adhesion and migration. Additionally, L-selectin has important signalling roles perhaps contributing to leukocyte activation and integrin-mediated adhesion. As chemokines are critically involved in leukocyte activation, we questioned whether L-selectin signaling affects chemokine receptor expression and function. We observed that while only 5-15% of freshly isolated lymphocytes expressed CXCR4 on the cell surface, intracellular CXCR4 was detectable in all cells. Engagement of L-selectin by antibody cross-linking or the L-selectin ligands fucoidan or sulfatide mobilized intracellular CXCR4 to significantly increase surface CXCR4 expression but did not affect CCR5, CCR7 or 2 integrin expression. L-selectin stimulation also inhibited SDF-1-induced CXCR4 internalization. The combined effects of L-selectin on CXCR4 trafficking are likely important in markedly enhancing cell activation by SDF-1. Blockade of SDF-1-induced CXCR4 internalization resulted in enhanced actin polymerization upon subsequent exposure to SDF-1. Physiologically more important, L-selectin stimulation increased SDF-1-induced lymphocyte adhesion and transendothelial migration, which were inhibited by anti-LFA-1 antibodies, tyrosine kinase inhibitors and pertussis toxin. To further corroborate the additive stimulating effects, L-selectin signalling and SDF-1 increased 2 integrin activation. Taken together, L-selectin mediated signals specifically enhance CXCR4 expression and function, suggesting a novel mechanism for the modulation of lymphocyte activation during cell adhesion and transmigration. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. Grundler, L. Brault, C. Gasser, A. N. Bullock, T. Dechow, S. Woetzel, V. Pogacic, A. Villa, S. Ehret, G. Berridge, et al. Dissection of PIM serine/threonine kinases in FLT3-ITD-induced leukemogenesis reveals PIM1 as regulator of CXCL12-CXCR4-mediated homing and migration J. Exp. Med., August 31, 2009; 206(9): 1957 - 1970. [Abstract] [Full Text] [PDF] D. J. Killock, M. Parsons, M. Zarrouk, S. M. Ameer-Beg, A. J. Ridley, D. O. Haskard, M. Zvelebil, and A. 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