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Blood, 1 November 2006, Vol. 108, No. 9, pp. 2906-2913. Prepublished online as a Blood First Edition Paper on July 18, 2006; DOI 10.1182/blood-2006-05-024638. This Article Full Text (PDF) All Versions of this Article: blood-2006-05-024638v1 108/9/2906    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 Arraes, S. M. A Articles by Cunha, F. Q Search for Related Content PubMed PubMed Citation Articles by Arraes, S. M. A Articles by Cunha, F. Q Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 22, 2006 Accepted June 24, 2006 Impaired neutrophil chemotaxis in sepsis associates with GRK expression and inhibition of actin assembly and tyrosine phosphorylation Sandra Mara A Arraes, Marta S Freitas, Simone V da Silva, Heitor A de Paula Neto, Jose Carlos Alves-Filho, Maria A Martins, Anibal Basile-Filho, Beatriz M Tavares-Murta, Christina Barja-Fidalgo, and Fernando Q Cunha* University of Sao Paulo, Brazil Universidade do Estado do Rio de Janeiro, Brazil Federal University of Triangulo Mineiro, Brazil * Corresponding author; email: fdqcunha{at}fmrp.usp.br. The deregulation of inflammatory response during sepsis seems to reflect the overproduction of mediators, which suppress leukocyte functions. We investigated the intracellular mechanisms underlying the inability of neutrophils from severe septic patients to migrate towards chemoattractants. Fifty-two septic patients and 15 volunteers were prospectively enrolled. Patients presented increased circulating levels of tumor necrosis factor-, interferon-, interleukin (IL)-8 and IL-10. Patients showed reduced neutrophil chemotaxis to formyl-methionyl-leucyl-phenylalanine (FMLP), leukotriene (LT)B4 or IL-8. No difference in the transcription or expression of the IL-8 receptor, CXCR1, was detected in neutrophils from controls and patients. However, septic neutrophils failed to increase tyrosine phosphorylation and actin polymerization in response to IL-8 or LTB4. In contrast, septic neutrophils, similar to controls, showed phagocytic activity that induced actin polymerization and augment in phosphotyrosine content. Treatment of control neutrophils with cytokines and lipopolysaccharide (LPS) to mimic endogenous septic environment inhibited actin polymerization and tyrosine phosphorylation in response to IL-8 or LTB4. High expression of G-protein-coupled receptor kinase (GRK)2 and GRK5 was detected in septic neutrophils and control cells treated with cytokines plus LPS. Data suggest that endogenous mediators produced during sepsis might continually activate circulating neutrophils, leading to GRK activation, which may induce neutrophil desensitization to chemoattractants. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Freitas, J. C. Alves-Filho, T. Victoni, T. Secher, H. P. Lemos, F. Sonego, F. Q. Cunha, and B. Ryffel IL-17 Receptor Signaling Is Required to Control Polymicrobial Sepsis J. Immunol., June 15, 2009; 182(12): 7846 - 7854. [Abstract] [Full Text] [PDF] J. C. Alves-Filho, A. Freitas, F. O. Souto, F. Spiller, H. Paula-Neto, J. S. Silva, R. T. Gazzinelli, M. M. Teixeira, S. H. Ferreira, and F. Q. Cunha Regulation of chemokine receptor by Toll-like receptor 2 is critical to neutrophil migration and resistance to polymicrobial sepsis PNAS, March 10, 2009; 106(10): 4018 - 4023. [Abstract] [Full Text] [PDF] D. Sorriento, M. Ciccarelli, G. Santulli, A. Campanile, G. G. Altobelli, V. Cimini, G. Galasso, D. Astone, F. Piscione, L. Pastore, et al. The G-protein-coupled receptor kinase 5 inhibits NF{kappa}B transcriptional activity by inducing nuclear accumulation of I{kappa}B{alpha} PNAS, November 18, 2008; 105(46): 17818 - 17823. [Abstract] [Full Text] [PDF] D. Dal-Secco, T. M. Cunha, A. Freitas, J. C. Alves-Filho, F. O. Souto, S. Y. Fukada, R. Grespan, N. M. N. Alencar, A. F. Neto, M. A. Rossi, et al. Hydrogen Sulfide Augments Neutrophil Migration through Enhancement of Adhesion Molecule Expression and Prevention of CXCR2 Internalization: Role of ATP-Sensitive Potassium Channels J. Immunol., September 15, 2008; 181(6): 4287 - 4298. [Abstract] [Full Text] [PDF] C. H. A. Nijboer, A. Kavelaars, A. Vroon, F. Groenendaal, F. van Bel, and C. J. Heijnen Low Endogenous G-Protein-Coupled Receptor Kinase 2 Sensitizes the Immature Brain to Hypoxia-Ischemia-Induced Gray and White Matter Damage J. Neurosci., March 26, 2008; 28(13): 3324 - 3332. [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]

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