HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 23, 24372-24386, June 4, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/23/24372    most recent M401364200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rose, J. J. Articles by Venkatesan, S. Search for Related Content PubMed PubMed Citation Articles by Rose, J. J. Articles by Venkatesan, S. Social Bookmarking                      What's this?

On the Mechanism and Significance of Ligand-induced Internalization of Human Neutrophil Chemokine Receptors CXCR1 and CXCR2^*

Jeremy J. Rose, John F. Foley, Philip M. Murphy¶, and Sundararajan Venkatesan||

From the Laboratory of Molecular Microbiology, Laboratory of Clinical Investigation, and ^¶Laboratory of Host Defenses, NIAID, National Institutes of Health, Bethesda, Maryland 20892

It is well established that leukocyte chemotactic receptors, a subset of G protein-coupled receptors, undergo endocytosis after stimulation by ligand. However, the significance of this phenomenon to cell motility and other important leukocyte functions induced by chemoattractants has not been clearly defined. Here we show that in primary human neutrophils, the threshold levels of agonist required for endocytosis of the chemotactic receptors CXCR1 and CXCR2 were 10-fold or higher than those needed for maximal chemotactic and calcium flux responses. Moreover, when stimulated by agonists at concentrations that are high enough for chemotaxis but too low for receptor endocytosis, neutrophil CXCR1 and CXCR2 could be reactivated in response to repeated application of the same agonist. Both receptors were excluded from Triton X-100-insoluble lipid rafts, and at high agonist concentrations were rapidly endocytosed by a clathrin/rab5/dynamin-dependent pathway. These data support the conclusion that neutrophil migration in response to CXCR1 or CXCR2 agonists is not dependent on endocytosis of CXCR1 or CXCR2. Rather than being integral to the process of cell migration, receptor endocytosis may be a terminal stop signal when cells reach the focus of inflammation where the chemoattractant concentrations are the highest.

Received for publication, February 6, 2004

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^|| To whom correspondence should be addressed: LMM, NIAID, National Institutes of Health, Bldg. 10, Rm. 6A05, Bethesda, MD 20892-1576. Tel.: 301-496-6359; Fax: 301-402-4122; E-mail: aradhana{at}helix.nih.gov or sv1s{at}nih.gov.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. M. Uriarte, D. W. Powell, G. C. Luerman, M. L. Merchant, T. D. Cummins, N. R. Jog, R. A. Ward, and K. R. McLeish Comparison of Proteins Expressed on Secretory Vesicle Membranes and Plasma Membranes of Human Neutrophils J. Immunol., April 15, 2008; 180(8): 5575 - 5581. [Abstract] [Full Text] [PDF]

				R. Samaniego, L. Sanchez-Martin, A. Estecha, and P. Sanchez-Mateos Rho/ROCK and myosin II control the polarized distribution of endocytic clathrin structures at the uropod of moving T lymphocytes J. Cell Sci., October 15, 2007; 120(20): 3534 - 3543. [Abstract] [Full Text] [PDF]

				I. C. Davis, A. Xu, Z. Gao, J. M. Hickman-Davis, P. Factor, W. M. Sullender, and S. Matalon Respiratory syncytial virus induces insensitivity to beta-adrenergic agonists in mouse lung epithelium in vivo Am J Physiol Lung Cell Mol Physiol, August 1, 2007; 293(2): L281 - L289. [Abstract] [Full Text] [PDF]

				M. Rey, A. Valenzuela-Fernandez, A. Urzainqui, M. Yanez-Mo, M. Perez-Martinez, P. Penela, F. Mayor Jr, and F. Sanchez-Madrid Myosin IIA is involved in the endocytosis of CXCR4 induced by SDF-1{alpha} J. Cell Sci., March 15, 2007; 120(6): 1126 - 1133. [Abstract] [Full Text] [PDF]

				F. Rios-Santos, J. C. Alves-Filho, F. O. Souto, F. Spiller, A. Freitas, C. M. C. Lotufo, M. B. P. Soares, R. R. dos Santos, M. M. Teixeira, and F. de Queiroz Cunha Down-regulation of CXCR2 on Neutrophils in Severe Sepsis Is Mediated by Inducible Nitric Oxide Synthase-derived Nitric Oxide Am. J. Respir. Crit. Care Med., March 1, 2007; 175(5): 490 - 497. [Abstract] [Full Text] [PDF]

				J. Sai, G. Walker, J. Wikswo, and A. Richmond The IL Sequence in the LLKIL Motif in CXCR2 Is Required for Full Ligand-induced Activation of Erk, Akt, and Chemotaxis in HL60 Cells J. Biol. Chem., November 24, 2006; 281(47): 35931 - 35941. [Abstract] [Full Text] [PDF]

				W. G. Tharp, R. Yadav, D. Irimia, A. Upadhyaya, A. Samadani, O. Hurtado, S-Y. Liu, S. Munisamy, D. M. Brainard, M. J. Mahon, et al. Neutrophil chemorepulsion in defined interleukin-8 gradients in vitro and in vivo J. Leukoc. Biol., March 1, 2006; 79(3): 539 - 554. [Abstract] [Full Text] [PDF]

				S. Pellme, M. Morgelin, H. Tapper, U.-H. Mellqvist, C. Dahlgren, and A. Karlsson Localization of human neutrophil interleukin-8 (CXCL-8) to organelle(s) distinct from the classical granules and secretory vesicles J. Leukoc. Biol., March 1, 2006; 79(3): 564 - 573. [Abstract] [Full Text] [PDF]

				F. R. Sheppard, M. R. Kelher, E. E. Moore, N. J. D. McLaughlin, A. Banerjee, and C. C. Silliman Structural organization of the neutrophil NADPH oxidase: phosphorylation and translocation during priming and activation J. Leukoc. Biol., November 1, 2005; 78(5): 1025 - 1042. [Abstract] [Full Text] [PDF]

				Y. Wu, P. Stabach, M. Michaud, and J. A. Madri Neutrophils Lacking Platelet-Endothelial Cell Adhesion Molecule-1 Exhibit Loss of Directionality and Motility in CXCR2-Mediated Chemotaxis J. Immunol., September 15, 2005; 175(6): 3484 - 3491. [Abstract] [Full Text] [PDF]

				D. Chakraborty, S. Banerjee, A. Sen, K. K. Banerjee, P. Das, and S. Roy Leishmania donovani Affects Antigen Presentation of Macrophage by Disrupting Lipid Rafts J. Immunol., September 1, 2005; 175(5): 3214 - 3224. [Abstract] [Full Text] [PDF]