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Science 1 November 1996:
Vol. 274. no. 5288, pp. 795 - 798
DOI: 10.1126/science.274.5288.795
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Reports

Decreased Resistance to Bacterial Infection and Granulocyte Defects in IAP-Deficient Mice

Frederik P. Lindberg, * Daniel C. Bullard, Tony E. Caver, Hattie D. Gresham, Arthur L. Beaudet, Eric J. Brown

Granulocyte [polymorphonuclear leucocyte (PMN)] migration to sites of infection and subsequent activation is essential for host defense. Gene-targeted mice deficient for integrin-associated protein (IAP, also termed CD47) succumbed to Escherichia coli peritonitis at inoccula survived by heterozygous littermates. In vivo, they had an early defect in PMN accumulation at the site of infection. In vitro, IAP-/- PMNs were deficient in beta 3 integrin-dependent ligand binding, activation of an oxidative burst, and Fc receptor-mediated phagocytosis. Thus, IAP plays a key role in host defense by participating both in PMN migration in response to bacterial infection and in PMN activation at extravascular sites.

F. P. Lindberg and E. J. Brown, Departments of Infectious Diseases and Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
D. C. Bullard, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
T. E. Caver, Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine, Columbia, MO 65212, USA.
H. D. Gresham, Research Service, Harry S. Truman Veterans Affairs Medical Center, Columbia, MO 65201, USA.
A. L. Beaudet, Department of Molecular and Human Genetics and Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA.
*   To whom correspondence should be addressed.

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The Thrombospondin Receptor Integrin-associated Protein (CD47) Functionally Couples to Heterotrimeric Gi.
W. A. Frazier, A.-G. Gao, J. Dimitry, J. Chung, E. J. Brown, F. P. Lindberg, and M. E. Linder (1999)
J. Biol. Chem. 274, 8554-8560
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The Vitronectin Receptor and its Associated CD47 Molecule Mediates Proinflammatory Cytokine Synthesis in Human Monocytes by Interaction with Soluble CD23.
P. Hermann, M. Armant, E. Brown, M. Rubio, H. Ishihara, D. Ulrich, R.G. Caspary, F.P. Lindberg, R. Armitage, C. Maliszewski, et al. (1999)
J. Cell Biol. 144, 767-775
   Abstract »    Full Text »    PDF »
Integrin-associated Protein Is a Ligand for the P84 Neural Adhesion Molecule.
P. Jiang, C. F. Lagenaur, and V. Narayanan (1999)
J. Biol. Chem. 274, 559-562
   Abstract »    Full Text »    PDF »
Highly Stoichiometric, Stable, and Specific Association of Integrin alpha 3beta 1 with CD151 Provides a Major Link to Phosphatidylinositol 4-Kinase, and May Regulate Cell Migration.
R. L. Yauch, F. Berditchevski, M. B. Harler, J. Reichner, and M. E. Hemler (1998)
Mol. Biol. Cell 9, 2751-2765
   Abstract »    Full Text »
A Role for the alpha vbeta 3 Integrin in the Transmigration of Monocytes.
D. Weerasinghe, K. P. McHugh, F. P. Ross, E. J. Brown, R. H. Gisler, and B. A. Imhof (1998)
J. Cell Biol. 142, 595-607
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I. Neutrophil adhesive interactions with intestinal epithelium.
C. A. Parkos (1997)
Am J Physiol Gastrointest Liver Physiol 273, G763-G768
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Thrombspondin Acts via Integrin-associated Protein to Activate the Platelet Integrin alpha IIbbeta 3.
J. Chung, A.-G. Gao, and W. A. Frazier (1997)
J. Biol. Chem. 272, 14740-14746
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Tumor Necrosis Factor-alpha Activation of the c-Jun N-terminal Kinase Pathway in Human Neutrophils. INTEGRIN INVOLVEMENT IN A PATHWAY LEADING FROM CYTOPLASMIC TYROSINE KINASES TO APOPTOSIS.
N. J. Avdi, J. A. Nick, B. B. Whitlock, M. A. Billstrom, P. M. Henson, G. L. Johnson, and G. S. Worthen (2001)
J. Biol. Chem. 276, 2189-2199
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Membrane Raft Association of CD47 Is Necessary for Actin Polymerization and Protein Kinase C theta Translocation in Its Synergistic Activation of T Cells.
R. A. Rebres, J. M. Green, M. I. Reinhold, M. Ticchioni, and E. J. Brown (2001)
J. Biol. Chem. 276, 7672-7680
   Abstract »    Full Text »    PDF »
Integrin Modulation by Lateral Association.
A. Woods and J. R. Couchman (2000)
J. Biol. Chem. 275, 24233-24236
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