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Blood, 15 June 2006, Vol. 107, No. 12, pp. 4857-4864. Prepublished online as a Blood First Edition Paper on February 28, 2006; DOI 10.1182/blood-2005-11-4398. This Article Full Text (PDF) All Versions of this Article: 2005-11-4398v1 107/12/4857    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 Fontana, S. Articles by Badolato, R. Search for Related Content PubMed PubMed Citation Articles by Fontana, S. Articles by Badolato, R. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 7, 2005 Accepted February 14, 2006 Innate immunity defects in Hermansky-Pudlak type 2 syndrome Stefania Fontana, Silvia Parolini, William Vermi, Sarah Booth, Federico Gallo, Marta Donini, Marzia Benassi, Francesca Gentili, Daniela Ferrari, Lucia D Notarangelo, Patrizia Cavadini, Emanuela Marcenaro, Stefano Dusi, Marco Cassatella, Fabio Facchetti, Gillian M Griffiths, Alessandro Moretta, Luigi D Notarangelo, and Raffaele Badolato* Istituto di Medicina Molecolare "Angelo Nocivelli", Clinica Pediatrica, University of Brescia, Brescia, Italy Dipartimento di Scienze Biomediche e Biotecnologie, University of Brescia, Brescia, Italy Cattedra di Anatomia Patologica, University of Brescia, Brescia, Italy Sir William Dunn School of Pathology, Oxford, United Kingdom Department di Pathology, Section of General Pathology, University of Verona, Verona, Italy Istituto Giannina Gaslini, Genova, Italy; Dipartimento di Medicina Sperimentale, University of Genova, Genova, Italy Dipartimento di Medicina Sperimentale, University of Genova, Genova, Italy; Centro di Eccellenza per le Ricerche Biomediche, University of Genova, Genova, Italy * Corresponding author; email: badolato{at}med.unibs.it. Adaptor protein-3 (AP-3) is an ubiquitous cytoplasmic complex that shuttles cargo proteins from the trans-Golgi and a tubular-endosomal compartment to endosome-lysosome related organelles. Lack of the 3A subunit of this complex causes Hermansky-Pudlak syndrome type 2, an autosomal recessive disease characterized by partial albinism, prolonged bleeding tendency and immunodeficiency. In order to investigate the pathogenesis of immunodeficiency, we studied NK cells and neutrophil functions in two previously unreported siblings affected by Hermansky-Pudlak type 2 syndrome. In both patients we observed a dramatic reduction of cytolytic activity of freshly isolated and of IL-2 activated NK cells. Levels of perforin were reduced in unstimulated NK cells, thereby accounting for the impairment of NK cytolitic activity. In addition, analysis of neutrophils in these patients demonstrated that intracellular elastase content was largely reduced while CD63 expression on plasma membrane was substantially increased. Taken together, these observations suggest that type 2 Hermansky-Pudlak syndrome is characterized by defects of innate immunity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M Huizing, B Pederson, R A Hess, A Griffin, A Helip-Wooley, W Westbroek, H Dorward, K J O'Brien, G Golas, E Tsilou, et al. Clinical and cellular characterisation of Hermansky-Pudlak syndrome type 6 J. Med. Genet., December 1, 2009; 46(12): 803 - 810. [Abstract] [Full Text] [PDF] L. Kallquist, M. Hansson, A.-M. Persson, H. Janssen, J. Calafat, H. Tapper, and I. Olsson The tetraspanin CD63 is involved in granule targeting of neutrophil elastase Blood, October 15, 2008; 112(8): 3444 - 3454. [Abstract] [Full Text] [PDF] M. Donini, S. Fontana, G. Savoldi, W. Vermi, L. Tassone, F. Gentili, E. Zenaro, D. Ferrari, L. D. Notarangelo, F. Porta, et al. G-CSF treatment of severe congenital neutropenia reverses neutropenia but does not correct the underlying functional deficiency of the neutrophil in defending against microorganisms Blood, June 1, 2007; 109(11): 4716 - 4723. [Abstract] [Full Text] [PDF] M. S. Horwitz, Z. Duan, B. Korkmaz, H.-H. Lee, M. E. Mealiffe, and S. J. Salipante Neutrophil elastase in cyclic and severe congenital neutropenia Blood, March 1, 2007; 109(5): 1817 - 1824. [Abstract] [Full Text] [PDF] K. Newell-Litwa, E. Seong, M. Burmeister, and V. Faundez Neuronal and non-neuronal functions of the AP-3 sorting machinery J. Cell Sci., February 15, 2007; 120(4): 531 - 541. [Abstract] [Full Text] [PDF] S. M. Di Pietro, J. M. Falcon-Perez, D. Tenza, S. R.G. Setty, M. S. Marks, G. Raposo, and E. C. Dell'Angelica BLOC-1 Interacts with BLOC-2 and the AP-3 Complex to Facilitate Protein Trafficking on Endosomes Mol. Biol. Cell, September 1, 2006; 17(9): 4027 - 4038. [Abstract] [Full Text] [PDF]

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