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Blood, 1 June 2007, Vol. 109, No. 11, pp. 4716-4723. Prepublished online as a Blood First Edition Paper on February 20, 2007; DOI 10.1182/blood-2006-09-045427. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-09-045427v1 109/11/4716    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 Donini, M. Articles by Badolato, R. Search for Related Content PubMed PubMed Citation Articles by Donini, M. Articles by Badolato, R. Related Collections Hematopoiesis and Stem Cells Immunobiology Related Articles in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS G-CSF treatment of severe congenital neutropenia reverses neutropenia but does not correct the underlying functional deficiency of the neutrophil in defending against microorganisms Marta Donini1, Stefania Fontana2, Gianfranco Savoldi2, William Vermi3, Laura Tassone2, Francesca Gentili3, Elena Zenaro1, Daniela Ferrari2, Lucia D. Notarangelo2, Fulvio Porta2, Fabio Facchetti3, Luigi D. Notarangelo2, Stefano Dusi1, and Raffaele Badolato2 1 Department of Pathology, Section of General Pathology, University of Verona, Italy; 2 Istituto di Medicina Molecolare "Angelo Nocivelli," and Clinica Pediatrica, University of Brescia, Italy; 3 Dipartimento Materno-Infantile e Tecnologie Biomediche, Cattedra di Anatomia Patologica, University of Brescia, Italy The treatment of children affected by severe congenital neutropenia (SCN) with G-CSF strongly reduces the risk of sepsis by reversing neutropenia. However, SCN patients who respond to the treatment with the growth factor still have an elevated risk of succumbing to sepsis. Because the disease is usually caused by heterozygous mutations of ELA2, a gene encoding for neutrophil elastase (NE), we have investigated in G-CSF–responder and nonresponder patients affected by SCN the expression of polypeptides that constitute the antimicrobial machinery of these cells. In peripheral blood–derived neutrophils of patients with heterozygous mutations of ELA2 who were treated with G-CSF, NE was nearly absent as detected by immunofluorescence and immunoblotting, suggesting that production of the mutant protein interferes with normal gene expression. This defect was associated with abnormal expression of other granule-associated proteins such as myeloperoxidase, lactoferrin, cathepsin G, and human-neutrophil-peptide. Moreover, in one patient with partial response to G-CSF, we observed an impairment of neutrophil antimicrobial activity against Candida albicans, and, to a lower extent against Escherichia coli. Thereby, we propose that the treatment with G-CSF is not sufficient to correct all of the functional deficiency of neutrophils, and this might account for the consistent risk of infections observed in SCN patients. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Articles in Blood Online: Expression of granule-associated proteins in neutrophils from patients with severe congenital neutropenia Mats Andersson, Jenny Karlsson, Göran Carlsson, and Katrin Pütsep Blood 2007 110: 2772-2773. [Full Text] [PDF] Response: ELA2 genotype-phenotype correlation to be expected in patients with severe congenital neutropenia Raffaele Badolato, Marta Donini, Gianfranco Savoldi, and Stefano Dusi Blood 2007 110: 2773-2774. [Full Text] [PDF] This article has been cited by other articles: C. S. Velu, A. M. Baktula, and H. L. Grimes Gfi1 regulates miR-21 and miR-196b to control myelopoiesis Blood, May 7, 2009; 113(19): 4720 - 4728. [Abstract] [Full Text] [PDF] L. A. Boxer, A. A. Bolyard, P. E. Newburger, M. A. Bonilla, G. Kannourakis, Y. Dror, D. C. Link, B. P. Alter, P. S. Rosenberg, and D. C. Dale Risk for Septic Death in Severe Congenital Neutropenia Blood (ASH Annual Meeting Abstracts), November 16, 2008; 112(11): 3548 - 3548. [Abstract] M. Andersson, J. Karlsson, G. Carlsson, and K. Putsep Expression of granule-associated proteins in neutrophils from patients with severe congenital neutropenia Blood, October 1, 2007; 110(7): 2772 - 2773. [Full Text] [PDF] R. Badolato, M. Donini, G. Savoldi, and S. Dusi Response: ELA2 genotype-phenotype correlation to be expected in patients with severe congenital neutropenia Blood, October 1, 2007; 110(7): 2773 - 2774. [Full Text] [PDF]

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