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This Article Full Text Full Text (PDF) 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 Harris, E. S. Articles by Lorant, D. E. Search for Related Content PubMed PubMed Citation Articles by Harris, E. S. Articles by Lorant, D. E. Related Collections Phagocytes Cell Adhesion and Motility Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 February 2001, Vol. 97, No. 3, pp. 767-776 PHAGOCYTES A novel syndrome of variant leukocyte adhesion deficiency involving defects in adhesion mediated by 1 and 2 integrins Estelle S. Harris, Ann O. Shigeoka, Wenhua Li, Roberta H. Adams, Stephen M. Prescott, Thomas M. McIntyre, Guy A. Zimmerman, and Diane E. Lorant From the Departments of Pediatrics, Internal Medicine, and Experimental Pathology, the Huntsman Cancer Institute, and the Program in Human Molecular Biology and Genetics, the University of Utah School of Medicine, Salt Lake City, UT. Leukocyte adhesion deficiency type I (LAD-1) is a disorder associated with severe and recurrent bacterial infections, impaired extravascular targeting and accumulation of myeloid leukocytes, altered wound healing, and significant morbidity that is caused by absent or greatly diminished surface expression of integrins of the 2 class. We report clinical features and analysis of functions of cells from a patient with a myelodysplastic syndrome and infectious complications similar to those in the severe form of LAD-1, but whose circulating neutrophils displayed normal levels of 2 integrins. Analysis of adhesion of these cells to immobilized ligands and to endothelial cells and assays of cell-cell aggregation and chemotaxis demonstrated a profound defect in adhesion mediated by 2 integrins indicative of a variant form of LAD-1. A novel cell line established from Epstein-Barr virus-transformed lymphoblasts from the subject demonstrated deficient 2 integrin-dependent adhesive function similar to that of the primary leukocytes. In addition, these cells had markedly impaired 1 integrin-dependent adhesion. Sequence analysis and electrophoretic mobility of 1 and 2 proteins from the cell line demonstrated that the defects were not a result of structural abnormalities in the integrin subunit chains themselves and suggest that the adhesive phenotype of these cells is due to one or more abnormalities of inside-out signaling mechanisms that regulate the activity of integrins of these classes. These features define a unique LAD-1 variant syndrome that may reveal important insights that are generally relevant to inside-out signaling of integrins, a molecular process that is as yet incompletely understood. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. W. Kuijpers, E. van de Vijver, M. A. J. Weterman, M. de Boer, A. T. J. Tool, T. K. van den Berg, M. Moser, M. E. Jakobs, K. Seeger, O. Sanal, et al. LAD-1/variant syndrome is caused by mutations in FERMT3 Blood, May 7, 2009; 113(19): 4740 - 4746. [Abstract] [Full Text] [PDF] R. Pasvolsky, S. W. Feigelson, S. S. Kilic, A. J. Simon, G. Tal-Lapidot, V. Grabovsky, J. R. Crittenden, N. Amariglio, M. Safran, A. M. Graybiel, et al. A LAD-III syndrome is associated with defective expression of the Rap-1 activator CalDAG-GEFI in lymphocytes, neutrophils, and platelets J. Exp. 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	Copyright © 2001 by American Society of Hematology         Online ISSN: 1528-0020