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Blood, 15 July 2004, Vol. 104, No. 2, pp. 444-452. Prepublished online as a Blood First Edition Paper on March 16, 2004; DOI 10.1182/blood-2003-10-3532. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-10-3532v1 104/2/444    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 Gulino, A. V. Articles by Badolato, R. Search for Related Content PubMed PubMed Citation Articles by Gulino, A. V. Articles by Badolato, R. Related Collections Immunobiology Phagocytes Cell Adhesion and Motility Signal Transduction Chemokines, Cytokines, and Interleukins Clinical Trials and Observations Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Altered leukocyte response to CXCL12 in patients with warts hypogammaglobulinemia, infections, myelokathexis (WHIM) syndrome Anna Virginia Gulino, Daniele Moratto, Silvano Sozzani, Patrizia Cavadini, Karel Otero, Laura Tassone, Luisa Imberti, Silvia Pirovano, Lucia D. Notarangelo, Roberta Soresina, Evelina Mazzolari, David L. Nelson, Luigi D. Notarangelo, and Raffaele Badolato From the Istituto di Medicina Molecolare "Angelo Nocivelli," Clinica Pediatrica, Section of General Pathology and Immunology, Universita' di Brescia, Italy; the Istituto di Ricerche Farmacologiche "Mario Negri," Milano, Italy; the Terzo Servizio Analisi, Spedali Civili, Brescia, Italy; and the Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD. The chemokine receptor CXCR4 and its functional ligand, CXCL12, are essential regulators of development and homeostasis of hematopoietic and lymphoid organs. Heterozygous truncating mutations in the CXCR4 intracellular tail cause a rare genetic disease known as WHIM syndrome (warts, hypogammaglobulinemia, infections, myelokathexis), whose pathophysiology remains unclear. We report CXCR4 function in 3 patients with WHIM syndrome carrying heterozygous truncating mutations of CXCR4. We show that CXCR4 gene mutations in WHIM patients do not affect cell surface expression of the chemokine receptor and its internalization upon stimulation with CXCL12. Moreover, no significant differences in calcium mobilization in response to CXCL12 are found. However, the chemotactic response of both polymorphonuclear cells and T lymphocytes in response to CXCL12 is increased. Furthermore, immunophenotypic analysis of circulating T and B lymphocytes reveals a decreased number of memory B cells and of naive T cells and an accumulation of effector memory T cells associated with a restricted T-cell repertoire. Based on our results, we suggest that the altered leukocyte response to CXCL12 may account for the pathologic retention of mature polymorphonuclear cells in the bone marrow (myelokathexis) and for an altered lymphocyte trafficking, which may cause the immunophenotyping abnormalities observed in WHIM patients. (Blood. 2004;104:444-452) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: The WHIMs of leukocytes Steven M. Holland Blood 2004 104: 301-302. [Full Text] [PDF] This article has been cited by other articles: B. Lagane, K. Y. C. Chow, K. Balabanian, A. Levoye, J. Harriague, T. Planchenault, F. Baleux, N. Gunera-Saad, F. Arenzana-Seisdedos, and F. Bachelerie CXCR4 dimerization and {beta}-arrestin-mediated signaling account for the enhanced chemotaxis to CXCL12 in WHIM syndrome Blood, July 1, 2008; 112(1): 34 - 44. [Abstract] [Full Text] [PDF] M. Carneiro-Sampaio and A. Coutinho Immunity to Microbes: Lessons from Primary Immunodeficiencies Infect. Immun., April 1, 2007; 75(4): 1545 - 1555. [Full Text] [PDF] T. Kawai, U. Choi, L. Cardwell, S. S. DeRavin, N. Naumann, N. L. Whiting-Theobald, G. F. Linton, J. Moon, P. M. Murphy, and H. L. 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