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J Biol Chem, Vol. 274, Issue 3, 1240-1247, January 15, 1999
From the Departments of Medicine and Pharmacology, Columbia
University College of Physicians and Surgeons,
New York, New York 10032
Phagocytosis requires actin assembly and
pseudopod extension, two cellular events that coincide spatially and
temporally. The signal transduction events underlying both processes
may be distinct. We tested whether phagocytic signaling resembles that of growth factor receptors, which induce actin polymerization via
activation of phosphatidylinositol 3-kinase (PI 3-kinase). Fc
A Requirement for Phosphatidylinositol 3-Kinase in Pseudopod
Extension
receptor-mediated phagocytosis was accompanied by a rapid increase in
the accumulation of phosphatidylinositol 3,4,5-trisphosphate in vivo, and addition of wortmannin (WM) or LY294002, two
inhibitors of PI 3-kinase(s), inhibited phagocytosis but not Fc
receptor-directed actin polymerization. However, both compounds
prevented maximal pseudopod extension, suggesting that PI 3-kinase
inhibition produced a limitation in membrane required for pseudopod
extension. Availability of plasma membrane was not limiting for
phagocytosis, because blockade of ingestion in the presence of WM was
not overcome by reducing the number of particles adhering to
macrophages. However, decreasing bead size, and hence the magnitude of
pseudopod extension required for particle engulfment, relieved the
inhibition of phagocytosis in the presence of WM or LY294002 by up to
80%. The block in phagocytosis of large particles occurred before
phagosomal closure, because both compounds inhibited spreading of
macrophages on substrate-bound IgG. Macrophage spreading on IgG was
accompanied by exocytic insertion of membrane from an intracellular
source, as measured by the dye FM1-43. These results indicate that one
or more isoforms of PI 3 kinase are required for maximal pseudopod
extension but not phagocytosis per se. We suggest that PI 3-kinase is
required for coordinating exocytic membrane insertion and pseudopod extension.
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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E. Garcia-Garcia, R. Rosales, and C. Rosales Phosphatidylinositol 3-kinase and extracellular signal-regulated kinase are recruited for Fc receptor-mediated phagocytosis during monocyte-to-macrophage differentiation J. Leukoc. Biol., July 1, 2002; 72(1): 107 - 114. [Abstract] [Full Text] [PDF]
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L.-A. H. Allen, C. Yang, and J. E. Pessin Rate and extent of phagocytosis in macrophages lacking vamp3 J. Leukoc. Biol., July 1, 2002; 72(1): 217 - 221. [Abstract] [Full Text] [PDF]
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O. Barreiro, M. Yanez-Mo, J. M. Serrador, M. C. Montoya, M. Vicente-Manzanares, R. Tejedor, H. Furthmayr, and F. Sanchez-Madrid Dynamic interaction of VCAM-1 and ICAM-1 with moesin and ezrin in a novel endothelial docking structure for adherent leukocytes J. Cell Biol., June 24, 2002; 157(7): 1233 - 1245. [Abstract] [Full Text] [PDF]
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 P. Maderna, D. C. Cottell, G. Berlasconi, N. A. Petasis, H. R. Brady, and C. Godson Lipoxins Induce Actin Reorganization in Monocytes and Macrophages But Not in Neutrophils : Differential Involvement of Rho GTPases Am. J. Pathol., June 1, 2002; 160(6): 2275 - 2283. [Abstract] [Full Text] [PDF]
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S. D. Kobayashi, J. M. Voyich, C. L. Buhl, R. M. Stahl, and F. R. DeLeo Global changes in gene expression by human polymorphonuclear leukocytes during receptor-mediated phagocytosis: Cell fate is regulated at the level of gene expression PNAS, May 14, 2002; 99(10): 6901 - 6906. [Abstract] [Full Text] [PDF]
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B. Hu, A. Punturieri, J. Todt, J. Sonstein, T. Polak, and J. L. Curtis Recognition and phagocytosis of apoptotic T cells by resident murine tissue macrophages require multiple signal transduction events J. Leukoc. Biol., May 1, 2002; 71(5): 881 - 889. [Abstract] [Full Text] [PDF]
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 P. P. Sanna, M. Cammalleri, F. Berton, C. Simpson, R. Lutjens, F. E. Bloom, and W. Francesconi Phosphatidylinositol 3-Kinase Is Required for the Expression But Not for the Induction or the Maintenance of Long-Term Potentiation in the Hippocampal CA1 Region J. Neurosci., May 1, 2002; 22(9): 3359 - 3365. [Abstract] [Full Text] [PDF]
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A. K. McNally and J. M. Anderson {beta}1 and {beta}2 Integrins Mediate Adhesion during Macrophage Fusion and Multinucleated Foreign Body Giant Cell Formation Am. J. Pathol., February 1, 2002; 160(2): 621 - 630. [Abstract] [Full Text] [PDF]
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R. Wiewrodt, A. P. Thomas, L. Cipelletti, M. Christofidou-Solomidou, D. A. Weitz, S. I. Feinstein, D. Schaffer, S. M. Albelda, M. Koval, and V. R. Muzykantov Size-dependent intracellular immunotargeting of therapeutic cargoes into endothelial cells Blood, February 1, 2002; 99(3): 912 - 922. [Abstract] [Full Text] [PDF]
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O. V. Vieira, R. J. Botelho, L. Rameh, S. M. Brachmann, T. Matsuo, H. W. Davidson, A. Schreiber, J. M. Backer, L. C. Cantley, and S. Grinstein Distinct roles of class I and class III phosphatidylinositol 3-kinases in phagosome formation and maturation J. Cell Biol., October 1, 2001; 155(1): 19 - 26. [Abstract] [Full Text] [PDF]
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J. G. Marshall, J. W. Booth, V. Stambolic, T. Mak, T. Balla, A. D. Schreiber, T. Meyer, and S. Grinstein Restricted Accumulation of Phosphatidylinositol 3-Kinase Products in a Plasmalemmal Subdomain during Fc{gamma} Receptor-mediated Phagocytosis J. Cell Biol., June 18, 2001; 153(7): 1369 - 1380. [Abstract] [Full Text] [PDF]
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H. Uchida, A. Kondo, Y. Yoshimura, Y. Mazaki, and H. Sabe PAG3/Pap{{alpha}}/KIAA0400, a GTPase-activating Protein for ADP-Ribosylation Factor (ARF), Regulates ARF6 in Fc{{gamma}} Receptor-mediated Phagocytosis of Macrophages J. Exp. Med., April 16, 2001; 193(8): 955 - 966. [Abstract] [Full Text] [PDF]
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M. G. Coppolino, M. Krause, P. Hagendorff, D. A. Monner, W. Trimble, S. Grinstein, J. Wehland, and A. S. Sechi Evidence for a molecular complex consisting of Fyb/SLAP, SLP-76, Nck, VASP and WASP that links the actin cytoskeleton to Fc{gamma} receptor signalling during phagocytosis J. Cell Sci., January 12, 2001; 114(23): 4307 - 4318. [Abstract] [Full Text] [PDF]
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A. Rupper, J. Rodriguez-Paris, B. Grove, and J. Cardelli p110-related PI 3-kinases regulate phagosome-phagosome fusion and phagosomal pH through a PKB/Akt dependent pathway in Dictyostelium J. Cell Sci., January 4, 2001; 114(7): 1283 - 1295. [Abstract] [PDF]
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R. May and L. Machesky Phagocytosis and the actin cytoskeleton J. Cell Sci., January 3, 2001; 114(6): 1061 - 1077. [Abstract] [PDF]
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D. Cox, B. M. Dale, M. Kashiwada, C. D. Helgason, and S. Greenberg A Regulatory Role for Src Homology 2 Domain-containing Inositol 5'-Phosphatase (SHIP) in Phagocytosis Mediated by Fc{{gamma}} Receptors and Complement Receptor 3 ({{alpha}}M{beta}2; CD11b/CD18) J. Exp. Med., December 27, 2000; 193(1): 61 - 72. [Abstract] [Full Text] [PDF]
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R. J. Botelho, M. Teruel, R. Dierckman, R. Anderson, A. Wells, J. D. York, T. Meyer, and S. Grinstein Localized Biphasic Changes in Phosphatidylinositol-4,5-Bisphosphate at Sites of Phagocytosis J. Cell Biol., December 18, 2000; 151(7): 1353 - 1368. [Abstract] [Full Text] [PDF]
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M. Amyere, B. Payrastre, U. Krause, P. V. D. Smissen, A. Veithen, and P. J. Courtoy Constitutive Macropinocytosis in Oncogene-transformed Fibroblasts Depends on Sequential Permanent Activation of Phosphoinositide 3-Kinase and Phospholipase C Mol. Biol. Cell, October 1, 2000; 11(10): 3453 - 3467. [Abstract] [Full Text]
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L. Serrander, P. Skarman, B. Rasmussen, W. Witke, D. P. Lew, K.-H. Krause, O. Stendahl, and O. Nu{beta}e Selective Inhibition of IgG-Mediated Phagocytosis in Gelsolin-Deficient Murine Neutrophils J. Immunol., September 1, 2000; 165(5): 2451 - 2457. [Abstract] [Full Text] [PDF]
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L. Bajno, X.-R. Peng, A. D. Schreiber, H.-P. Moore, W. S. Trimble, and S. Grinstein Focal Exocytosis of VAMP3-containing Vesicles at Sites of Phagosome Formation J. Cell Biol., May 1, 2000; 149(3): 697 - 706. [Abstract] [Full Text] [PDF]
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M. Emoto, J. K. Klarlund, S. B. Waters, V. Hu, J. M. Buxton, A. Chawla, and M. P. Czech A Role for Phospholipase D in GLUT4 Glucose Transporter Translocation J. Biol. Chem., March 15, 2000; 275(10): 7144 - 7151. [Abstract] [Full Text] [PDF]
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D. J. Lee, D. Cox, J. Li, and S. Greenberg Rac1 and Cdc42 Are Required for Phagocytosis, but Not NF-kappa B-dependent Gene Expression, in Macrophages Challenged with Pseudomonas aeruginosa J. Biol. Chem., January 7, 2000; 275(1): 141 - 146. [Abstract] [Full Text] [PDF]
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E. S. Gold, D. M. Underhill, N. S. Morrissette, J. Guo, M. A. McNiven, and A. Aderem Dynamin 2 Is Required for Phagocytosis in Macrophages J. Exp. Med., December 20, 1999; 190(12): 1849 - 1856. [Abstract] [Full Text] [PDF]
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M. G. Coppolino, C. Kong, M. Mohtashami, A. D. Schreiber, J. H. Brumell, B. B. Finlay, S. Grinstein, and W. S. Trimble Requirement for N-Ethylmaleimide-sensitive Factor Activity at Different Stages of Bacterial Invasion and Phagocytosis J. Biol. Chem., February 9, 2001; 276(7): 4772 - 4780. [Abstract] [Full Text] [PDF]
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D. J. Hackam, R. J. Botelho, C. Sjolin, O. D. Rotstein, J. M. Robinson, A. D. Schreiber, and S. Grinstein Indirect Role for COPI in the Completion of Fcgamma Receptor-mediated Phagocytosis J. Biol. Chem., May 18, 2001; 276(21): 18200 - 18208. [Abstract] [Full Text] [PDF]
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