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Blood, 1 January 2005, Vol. 105, No. 1, pp. 170-177. Prepublished online as a Blood First Edition Paper on August 24, 2004; DOI 10.1182/blood-2004-02-0498. This Article Full Text (PDF) All Versions of this Article: 2004-02-0498v1 105/1/170    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 Spijkers, P. P Articles by Lenting, P. J Search for Related Content PubMed PubMed Citation Articles by Spijkers, P. P Articles by Lenting, P. J Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 9, 2004 Accepted August 13, 2004 LDL-Receptor related protein regulates 2-integrin mediated leukocyte adhesion Patricia P Spijkers, Paula da Costa Martins, Erik Westein, Carl G Gahmberg, Jaap J Zwaginga, and Peter J Lenting* Laboratory for Thrombosis and Haemostasis, Department of Haematology, University Medical Center Utrecht, Utrecht, The Netherlands Department of Experimental Immunohaematology, Sanquin Research, Amsterdam, The Netherlands Department of Biological and Environmental Sciences, Division of Biochemistry, University of Helsinki, Helsinki, Finland * Corresponding author; email: p.j.lenting{at}lab.azu.nl. 2-integrin clustering upon activation is a key event in leukocyte adhesion to the endothelium during the inflammatory response. Searching for molecular mechanisms leading to this clustering, we have identified LDL-receptor related protein (LRP) as a new partner for 2-integrins at the leukocyte surface. Immobilized recombinant LRP fragments served as an adhesive surface for blood-derived leukocytes and the U937 cell line. This adhesion was decreased up to 95 % in the presence of antibodies against 2-integrins, pointing to these integrins as potential partners for LRP. Using purified proteins, LRP indeed associated with the M2 complex and the M and L I-domains (KD,app= 0.5 µM). Immunoprecipitation experiments and confocal microscopy revealed that endogenously expressed LRP and L2 colocalized in monocytes and U937 cells. Furthermore, activation of U937 cells resulted in clustering of L2 and LRP to similar regions at the cellular surface, indicating potential cooperation between both proteins. This was confirmed by the lack of L2 clustering in U937 cells treated by antisense oligonucleotides to downregulate LRP. In addition, the absence of LRP resulted in complete abrogation of 2-integrin-dependent adhesion to endothelial cells in a perfusion system, demonstrating the presence of a previously unrecognised link between LRP and leukocyte function. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M.-L. Tang, A. Vararattanavech, and S.-M. Tan Urokinase-type Plasminogen Activator Receptor Induces Conformational Changes in the Integrin {alpha}M{beta}2 Headpiece and Reorientation of Its Transmembrane Domains J. Biol. Chem., September 12, 2008; 283(37): 25392 - 25403. [Abstract] [Full Text] [PDF] A. P. Lillis, L. B. Van Duyn, J. E. Murphy-Ullrich, and D. K. Strickland LDL Receptor-Related Protein 1: Unique Tissue-Specific Functions Revealed by Selective Gene Knockout Studies Physiol Rev, July 1, 2008; 88(3): 887 - 918. [Abstract] [Full Text] [PDF] S. Dedieu, B. Langlois, J. Devy, B. Sid, P. Henriet, H. Sartelet, G. Bellon, H. Emonard, and L. Martiny LRP-1 Silencing Prevents Malignant Cell Invasion despite Increased Pericellular Proteolytic Activities Mol. Cell. Biol., May 1, 2008; 28(9): 2980 - 2995. [Abstract] [Full Text] [PDF] S. C. Fagerholm, M. Varis, M. Stefanidakis, T. J. Hilden, and C. G. Gahmberg {alpha}-Chain phosphorylation of the human leukocyte CD11b/CD18 (Mac-1) integrin is pivotal for integrin activation to bind ICAMs and leukocyte extravasation Blood, November 15, 2006; 108(10): 3379 - 3386. [Abstract] [Full Text] [PDF] S. S. Li, Z. Liu, M. Uzunel, and K.-G. Sundqvist Endogenous thrombospondin-1 is a cell-surface ligand for regulation of integrin-dependent T-lymphocyte adhesion Blood, November 1, 2006; 108(9): 3112 - 3120. [Abstract] [Full Text] [PDF] A. Gaultier, A. M. Salicioni, S. Arandjelovic, and S. L. Gonias Regulation of the Composition of the Extracellular Matrix by Low Density Lipoprotein Receptor-related Protein-1: ACTIVITIES BASED ON REGULATION OF mRNA EXPRESSION J. Biol. Chem., March 17, 2006; 281(11): 7332 - 7340. [Abstract] [Full Text] [PDF]

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