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Blood, 15 May 2004, Vol. 103, No. 10, pp. 3915-3923. Prepublished online as a Blood First Edition Paper on February 5, 2004; DOI 10.1182/blood-2003-11-3940. This Article Full Text (PDF) All Versions of this Article: 2003-11-3940v1 103/10/3915    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 Kuijpers, T W Articles by Barth, P G Search for Related Content PubMed PubMed Citation Articles by Kuijpers, T W Articles by Barth, P G Related Collections Related Letter in Blood Online Social Bookmarking                   What's this? Submitted December 3, 2003 Accepted January 18, 2004 Neutrophils in Barth Syndrome (BTHS) avidly bind Annexin-V in the absence of apoptosis T W Kuijpers*, N A Maianski, A T Tool, K Becker, B Plecko, F Valianpour, R J Wanders, R Pereira, J Van Hove, A J Verhoeven, D Roos, F Baas, and P G Barth Emma Children Hospital, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands Emma Children Hospital, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands; Sanquin Research at CLB, and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands Sanquin Research at CLB, and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands Dept. of Pediatric Cardiology, University Children Hospital, Kiel, Germany Dept. of Pediatrics, University Hospital, Graz, Austria Dept. of Pediatrics, Medical Centre Rijnmond-Zuid, Rotterdam, The Netherlands Dept. of Pediatrics, University Hospital Leuven, Leuven, Belgium * Corresponding author; email: t.w.kuijpers{at}amc.uva.nl. Barth Syndrome (BTHS) is a rare X-linked disease characterized by a triad of dilated cardiomyopathy, skeletal myopathy, and neutropenia. The disease is associated with mutations of the TAZ gene, resulting in defective cardiolipin (CL), an important inner mitochondrial membrane component. Untreated boys die in infancy or early childhood from septicemia or cardiac failure. To date neutrophil function has never been studied. Directed motility and killing activity of neutrophils was investigated in 7 BTHS patients and found normal in those tested. The circulating neutrophils and eosinophils (but not monocytes or lymphocytes) showed Annexin-V binding, suggesting phosphatidylserine (PS) exposure due to apoptosis. However, caspase activity was absent in fresh BTHS cells. Unexpectedly, the near absence of CL did also not impact the mitochondrial mass and shape in fresh BTHS neutrophils, nor mitochondrial clustering and Bax translocation upon apoptosis. Annexin-V binding to BTHS neutrophils was not caused by phospholipid scrambling. Moreover, freshly purified BTHS neutrophils were not phagocytosed by macrophages. In sum, a massive number of circulating Annexin-V-binding neutrophils in the absence of apoptosis can be demonstrated in BTHS. These neutrophils expose an alternative substrate for Annexin-V different from PS and not recognized by macrophages, excluding early clearance as an explanation for the neutropenia. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Letter in Blood Online: Phosphatidylserine externalization in cardiolipin-deficient cells Bengt Fadeel, Maria B. Karpova, Mari Enoksson, Sten Orrenius, and Taco W. Kuijpers Blood 2004 104: 1582-1584. [Full Text] [PDF] This article has been cited by other articles: B. J. van Raam, R. van Bruggen, A. T. J. Tool, M. H. Jansen, A. Warris, S. Jolles, and T. W. Kuijpers Nuclear factor-{kappa}B is not essential for NADPH oxidase activity in neutrophils from anhidrotic ectodermal dysplasia patients Blood, May 21, 2009; 113(21): 5362 - 5363. [Full Text] [PDF] M. Schlame Thematic Review Series: Glycerolipids. Cardiolipin synthesis for the assembly of bacterial and mitochondrial membranes J. Lipid Res., August 1, 2008; 49(8): 1607 - 1620. [Abstract] [Full Text] [PDF] T. W. Kuijpers, R. v. Bruggen, N. Kamerbeek, A. T. J. Tool, G. Hicsonmez, A. Gurgey, A. Karow, A. J. Verhoeven, K. Seeger, O. Sanal, et al. Natural history and early diagnosis of LAD-1/variant syndrome Blood, April 15, 2007; 109(8): 3529 - 3537. [Abstract] [Full Text] [PDF] T. W. Kuijpers, M. Alders, A. T. J. Tool, C. Mellink, D. Roos, and R. C. M. Hennekam Hematologic abnormalities in Shwachman Diamond syndrome: lack of genotype-phenotype relationship Blood, July 1, 2005; 106(1): 356 - 361. [Abstract] [Full Text] [PDF] F. Valianpour, V. Mitsakos, D. Schlemmer, J. A. Towbin, J. M. Taylor, P. G. Ekert, D. R. Thorburn, A. Munnich, R. J. A. Wanders, P. G. Barth, et al. Monolysocardiolipins accumulate in Barth syndrome but do not lead to enhanced apoptosis J. Lipid Res., June 1, 2005; 46(6): 1182 - 1195. [Abstract] [Full Text] [PDF] P. Massullo, L. J. Druhan, B. A. Bunnell, M. G. Hunter, J. M. Robinson, C. B. Marsh, and B. R. Avalos Aberrant subcellular targeting of the G185R neutrophil elastase mutant associated with severe congenital neutropenia induces premature apoptosis of differentiating promyelocytes Blood, May 1, 2005; 105(9): 3397 - 3404. [Abstract] [Full Text] [PDF] H. Kenis, H. van Genderen, A. Bennaghmouch, H. A. Rinia, P. Frederik, J. Narula, L. Hofstra, and C. P. M. Reutelingsperger Cell Surface-expressed Phosphatidylserine and Annexin A5 Open a Novel Portal of Cell Entry J. Biol. Chem., December 10, 2004; 279(50): 52623 - 52629. [Abstract] [Full Text] [PDF]

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