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Clinica Pediatrica,
Cattedra di Chimica, and
Sezione di Patologia Generale ed Immunologia, Universita’ di Brescia, Brescia, Italy;
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Dipartimento di Patologia e Medicina Sperimentale e Clinica, Universita’ di Udine, Udine, Italy;
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Servizio di Immunologia Clinica, Spedali Civili, Brescia, Italy; and
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Istituto Ricerche Farmacologiche "Mario Negri," Milan, Italy
Wiskott-Aldrich syndrome (WAS) is an X-linked disorder
characterized by trombocytopenia, eczema, and progressive decline of
the immune function. In addition, lymphocytes and platelets from WAS
patients have morphologic abnormalities. Since chemokines may induce
morphologic changes and migration of leukocytes, we investigated the
monocyte response to chemoattractants in cells from WAS patients with
an identified mutation in the WAS protein gene. Here, we report that
monocytes derived from four patients with molecularly defined typical
WAS have a severely impaired migration in response to FMLP and to the
chemokines monocyte chemoattractant protein-1 (MCP-1) and macrophage
inflammatory protein-1
compared with normal donors. Conversely,
neither MCP-1 binding to monocytes nor induction of the respiratory
burst by MCP-1 and FMLP is significantly different between WAS patients
and normal donors. Within a few minutes of stimulation, monocytes
respond to chemokines with increased expression of adhesion molecules
and with morphologic changes such as cell polarization. Although
up-regulation of CD11b/CD18 expression following stimulation with FMLP
or MCP-1 is preserved in WAS patients, cell polarization is
dramatically decreased. Staining of F-actin by FITC-phalloidin in
monocytes stimulated with chemoattractants shows F-actin to have a
rounded shape in WAS patients, as opposed to the polymorphic
distribution of F-actin in the polarized monocytes from healthy donors.
These results suggest that WAS protein is involved in the monocyte
response to the chemokines MCP-1 and macrophage inflammatory
protein-1.
This article has been cited by other articles:
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H. Ozsahin, M. Cavazzana-Calvo, L. D. Notarangelo, A. Schulz, A. J. Thrasher, E. Mazzolari, M. A. Slatter, F. Le Deist, S. Blanche, P. Veys, et al. Long-term outcome following hematopoietic stem-cell transplantation in Wiskott-Aldrich syndrome: collaborative study of the European Society for Immunodeficiencies and European Group for Blood and Marrow Transplantation Blood, January 1, 2008; 111(1): 439 - 445. [Abstract] [Full Text] [PDF]
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S. Tsuboi and J. Meerloo Wiskott-Aldrich Syndrome Protein Is a Key Regulator of the Phagocytic Cup Formation in Macrophages J. Biol. Chem., November 23, 2007; 282(47): 34194 - 34203. [Abstract] [Full Text] [PDF]
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S. Tsuboi A Complex of Wiskott-Aldrich Syndrome Protein with Mammalian Verprolins Plays an Important Role in Monocyte Chemotaxis. J. Immunol., June 1, 2006; 176(11): 6576 - 6585. [Abstract] [Full Text] [PDF]
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M. D. Gallego, M. A. de la Fuente, I. M. Anton, S. Snapper, R. Fuhlbrigge, and R. S. Geha WIP and WASP play complementary roles in T cell homing and chemotaxis to SDF-1{alpha} Int. Immunol., February 1, 2006; 18(2): 221 - 232. [Abstract] [Full Text] [PDF]
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S. B. Snapper, P. Meelu, D. Nguyen, B. M. Stockton, P. Bozza, F. W. Alt, F. S. Rosen, U. H. von Andrian, and C. Klein WASP deficiency leads to global defects of directed leukocyte migration in vitro and in vivo J. Leukoc. Biol., June 1, 2005; 77(6): 993 - 998. [Abstract] [Full Text] [PDF]
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S. de Noronha, S. Hardy, J. Sinclair, M. P. Blundell, J. Strid, O. Schulz, J. Zwirner, G. E. Jones, D. R. Katz, C. Kinnon, et al. Impaired dendritic-cell homing in vivo in the absence of Wiskott-Aldrich syndrome protein Blood, February 15, 2005; 105(4): 1590 - 1597. [Abstract] [Full Text] [PDF]
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L. Westerberg, M. Larsson, S. J. Hardy, C. Fernandez, A. J. Thrasher, and E. Severinson Wiskott-Aldrich syndrome protein deficiency leads to reduced B-cell adhesion, migration, and homing, and a delayed humoral immune response Blood, February 1, 2005; 105(3): 1144 - 1152. [Abstract] [Full Text] [PDF]
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Y. Jin, C. Mazza, J. R. Christie, S. Giliani, M. Fiorini, P. Mella, F. Gandellini, D. M. Stewart, Q. Zhu, D. L. Nelson, et al. Mutations of the Wiskott-Aldrich Syndrome Protein (WASP): hotspots, effect on transcription, and translation and phenotype/genotype correlation Blood, December 15, 2004; 104(13): 4010 - 4019. [Abstract] [Full Text] [PDF]
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S. Burns, G. O. Cory, W. Vainchenker, and A. J. Thrasher Mechanisms of WASp-mediated hematologic and immunologic disease Blood, December 1, 2004; 104(12): 3454 - 3462. [Abstract] [Full Text] [PDF]
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R. Badolato Leukocyte circulation: one-way or round-trip? Lessons from primary immunodeficiency patients J. Leukoc. Biol., July 1, 2004; 76(1): 1 - 6. [Abstract] [Full Text] [PDF]
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S. Fais and W. Malorni Leukocyte uropod formation and membrane/cytoskeleton linkage in immune interactions J. Leukoc. Biol., May 1, 2003; 73(5): 556 - 563. [Abstract] [Full Text] [PDF]
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C. Klein, D. Nguyen, C.-H. Liu, A. Mizoguchi, A. K. Bhan, H. Miki, T. Takenawa, F. S. Rosen, F. W. Alt, R. C. Mulligan, et al. Gene therapy for Wiskott-Aldrich syndrome: rescue of T-cell signaling and amelioration of colitis upon transplantation of retrovirally transduced hematopoietic stem cells in mice Blood, March 15, 2003; 101(6): 2159 - 2166. [Abstract] [Full Text] [PDF]
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M. Fiorini, W. Vermi, F. Facchetti, D. Moratto, G. Alessandri, L. Notarangelo, A. Caruso, P. Grigolato, A. G. Ugazio, L. D. Notarangelo, et al. Defective migration of monocyte-derived dendritic cells in LAD-1 immunodeficiency J. Leukoc. Biol., October 1, 2002; 72(4): 650 - 656. [Abstract] [Full Text] [PDF]
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L. Westerberg, G. Greicius, S. B. Snapper, P. Aspenstrom, and E. Severinson Cdc42, Rac1, and the Wiskott-Aldrich syndrome protein are involved in the cytoskeletal regulation of B lymphocytes Blood, August 15, 2001; 98(4): 1086 - 1094. [Abstract] [Full Text] [PDF]
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E. Haddad, J. L. Zugaza, F. Louache, N. Debili, C. Crouin, K. Schwarz, A. Fischer, W. Vainchenker, and J. Bertoglio The interaction between Cdc42 and WASP is required for SDF-1-induced T-lymphocyte chemotaxis Blood, January 1, 2001; 97(1): 33 - 38. [Abstract] [Full Text] [PDF]
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G. E. Jones Cellular signaling in macrophage migration and chemotaxis J. Leukoc. Biol., November 1, 2000; 68(5): 593 - 602. [Abstract] [Full Text]
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S. Linder, H. Higgs, K. Hufner, K. Schwarz, U. Pannicke, and M. Aepfelbacher The Polarization Defect of Wiskott-Aldrich Syndrome Macrophages Is Linked to Dislocalization of the Arp2/3 Complex J. Immunol., July 1, 2000; 165(1): 221 - 225. [Abstract] [Full Text] [PDF]
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D. N. Savoy, D. D. Billadeau, and P. J. Leibson Cutting Edge: WIP, a Binding Partner for Wiskott-Aldrich Syndrome Protein, Cooperates with Vav in the Regulation of T Cell Activation J. Immunol., March 15, 2000; 164(6): 2866 - 2870. [Abstract] [Full Text] [PDF]
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L. Tian, D. L. Nelson, and D. M. Stewart Cdc42-interacting Protein 4 Mediates Binding of the Wiskott-Aldrich Syndrome Protein to Microtubules J. Biol. Chem., March 10, 2000; 275(11): 7854 - 7861. [Abstract] [Full Text] [PDF]
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S. L. Rawlings, G. M. Crooks, D. Bockstoce, L. W. Barsky, R. Parkman, and K. I. Weinberg Spontaneous Apoptosis in Lymphocytes From Patients With Wiskott-Aldrich Syndrome: Correlation of Accelerated Cell Death and Attenuated Bcl-2 Expression Blood, December 1, 1999; 94(11): 3872 - 3882. [Abstract] [Full Text] [PDF]
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J. Zhang, A. Shehabeldin, L. A.G. da Cruz, J. Butler, A.-K. Somani, M. McGavin, I. Kozieradzki, A. O. dos Santos, A. Nagy, S. Grinstein, et al. Antigen Receptor-Induced Activation and Cytoskeletal Rearrangement Are Impaired in Wiskott-Aldrich Syndrome Protein-Deficient Lymphocytes J. Exp. Med., November 1, 1999; 190(9): 1329 - 1342. [Abstract] [Full Text] [PDF]
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 S. Linder, D. Nelson, , M. Weiss, and M. Aepfelbacher Wiskott-Aldrich syndrome protein regulates podosomes in primary human macrophages PNAS, August 17, 1999; 96(17): 9648 - 9653. [Abstract] [Full Text] [PDF]
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E. Haddad, E. Cramer, C. Riviere, P. Rameau, F. Louache, J. Guichard, D. L. Nelson, A. Fischer, W. Vainchenker, and N. Debili The Thrombocytopenia of Wiskott Aldrich Syndrome Is Not Related to a Defect in Proplatelet Formation Blood, July 15, 1999; 94(2): 509 - 518. [Abstract] [Full Text] [PDF]
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G. Vaduva, N. Martinez-Quiles, I. M. Anton, N. C. Martin, R. S. Geha, A. K. Hopper, and N. Ramesh The Human WASP-interacting Protein, WIP, Activates the Cell Polarity Pathway in Yeast J. Biol. Chem., June 11, 1999; 274(24): 17103 - 17108. [Abstract] [Full Text] [PDF]
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D. M. Stewart, L. Tian, and D. L. Nelson Mutations That Cause the Wiskott-Aldrich Syndrome Impair the Interaction of Wiskott-Aldrich Syndrome Protein (WASP) with WASP Interacting Protein J. Immunol., April 15, 1999; 162(8): 5019 - 5024. [Abstract] [Full Text] [PDF]
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