SEARCH:   Advanced

Blood, 1 January 2007, Vol. 109, No. 1, pp. 176-184. Prepublished online as a Blood First Edition Paper on September 7, 2006; DOI 10.1182/blood-2006-01-029199. This Article Full Text Full Text (PDF) Supplemental Table and Figure All Versions of this Article: blood-2006-01-029199v1 109/1/176    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 Hyduk, S. J. Articles by Cybulsky, M. I. Search for Related Content PubMed PubMed Citation Articles by Hyduk, S. J. Articles by Cybulsky, M. I. Related Collections Immunobiology Cell Adhesion and Motility Signal Transduction Immunotherapy Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Phospholipase C, calcium, and calmodulin are critical for 4ß1 integrin affinity up-regulation and monocyte arrest triggered by chemoattractants Sharon J. Hyduk1,3, Jason R. Chan,1,3, Stewart T. Duffy1,3, Mian Chen1,3, Mark D. Peterson2,3, Thomas K. Waddell2,3, Genevieve C. Digby1,3, Katalin Szaszi2,3, Andras Kapus1,3, and Myron I. Cybulsky1,3, 1 Department of Laboratory Medicine and Pathobiology, University of Toronto, ON, Canada; 2 Department of Surgery, University of Toronto, ON, Canada; 3 Toronto General Research Institute, University Health Network, Toronto, ON, Canada During inflammation, monocytes roll on activated endothelium and arrest after stimulation by proteoglycan-bound chemokines and other chemoattractants. We investigated signaling pathways downstream of G protein–coupled receptors (GPCRs) that are relevant to 4ß1 integrin affinity up-regulation using formyl peptide receptor-transfected U937 cells stimulated with fMLP or stromal-derived factor-1 and human peripheral blood monocytes stimulated with multiple chemokines or chemoattractants. The up-regulation of soluble LDV peptide or vascular cell adhesion molecule-1 (VCAM-1) binding by these stimuli was critically dependent on activation of phospholipase C (PLC), inositol 1,4,5-triphosphate receptors, increased intracellular calcium, influx of extracellular calcium, and calmodulin, suggesting that this signaling pathway is required for 4 integrins to assume a high-affinity conformation. In fact, a rise in intracellular calcium following treatment with thapsigargin or ionomycin was sufficient to induce binding of ligand. Blockade of p44/42 and p38 mitogen-activated protein (MAP) kinases, phosphoinositide 3-kinase, or protein kinase C (PKC) signaling did not inhibit chemoattractant-induced LDV or VCAM-1 binding. However, activation of PKC by phorbol ester up-regulated 4ß1 affinity with kinetics distinct from those of GPCR signaling. A critical role for PLC and calmodulin was also established for leukocyte arrest and adhesion strengthening. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Zarbock and K. Ley Mechanisms and Consequences of Neutrophil Interaction with the Endothelium Am. J. Pathol., January 1, 2008; 172(1): 1 - 7. [Abstract] [Full Text] [PDF] A. Zarbock, T. L. Deem, T. L. Burcin, and K. Ley G{alpha}i2 is required for chemokine-induced neutrophil arrest Blood, November 15, 2007; 110(10): 3773 - 3779. [Abstract] [Full Text] [PDF] H. Ghandour, X. Cullere, A. Alvarez, F. W. Luscinskas, and T. N. Mayadas Essential role for Rap1 GTPase and its guanine exchange factor CalDAG-GEFI in LFA-1 but not VLA-4 integrin mediated human T-cell adhesion Blood, November 15, 2007; 110(10): 3682 - 3690. [Abstract] [Full Text] [PDF] E. Manevich, V. Grabovsky, S. W. Feigelson, and R. Alon Talin 1 and Paxillin Facilitate Distinct Steps in Rapid VLA-4-mediated Adhesion Strengthening to Vascular Cell Adhesion Molecule 1 J. Biol. Chem., August 31, 2007; 282(35): 25338 - 25348. [Abstract] [Full Text] [PDF]

	Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020