| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,
,
* Inflammation Program, Division of Infectious Diseases, Departments of Internal Medicine, and
Physiology and Biophysics, and
Graduate Programs in Immunology and Molecular Biology, Carver College of Medicine and Veterans Affairs Medical Center, University of Iowa, Iowa City, IA, 52241; and
Center for Rheumatology and Immunology, Laval University, Quebec City, Quebec, Canada
Phagocytosis is a fundamental feature of the innate immune system, required for antimicrobial defense, resolution of inflammation, and tissue remodeling. Furthermore, phagocytosis is coupled to a diverse range of cytotoxic effector mechanisms, including the respiratory burst, secretion of inflammatory mediators and Ag presentation. Phospholipase D (PLD) has been linked to the regulation of phagocytosis and subsequent effector responses, but the identity of the PLD isoform(s) involved and the molecular mechanisms of activation are unknown. We used primary human macrophages and human THP-1 promonocytes to characterize the role of PLD in phagocytosis. Macrophages, THP-1 cells, and other human myelomonocytic cells expressed both PLD1 and PLD2 proteins. Phagocytosis of complement-opsonized zymosan was associated with stimulation of the activity of both PLD1 and PLD2, as demonstrated by a novel immunoprecipitation-in vitro PLD assay. Transfection of dominant-negative PLD1 or PLD2 each inhibited the extent of phagocytosis (by 55–65%), and their combined effects were additive (reduction of 91%). PLD1 and PLD2 exhibited distinct localizations in resting macrophages and those undergoing phagocytosis, and only PLD1 localized to the phagosome membrane. The COS-7 monkey fibroblast cell line, which has been used as a heterologous system for the analysis of receptor-mediated phagocytosis, expressed PLD2 but not PLD1. These data support a model in which macrophage phagocytosis is coordinately regulated by both PLD1 and PLD2, with isoform-specific localization. Human myelomonocytic cell lines accurately model PLD-dependent signal transduction events required for phagocytosis, but the heterologous COS cell system does not.
This article has been cited by other articles:
|
|
 |
|
  J. Jongstra-Bilen, A. Puig Cano, M. Hasija, H. Xiao, C. I. E. Smith, and M. I. Cybulsky Dual Functions of Bruton's Tyrosine Kinase and Tec Kinase during Fc{gamma} Receptor-Induced Signaling and Phagocytosis J. Immunol., July 1, 2008; 181(1): 288 - 298. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. C. Chae, J. H. Kim, K. L. Kim, H. W. Kim, H. Y. Lee, W. D. Heo, T. Meyer, P.-G. Suh, and S. H. Ryu Phospholipase D Activity Regulates Integrin-mediated Cell Spreading and Migration by Inducing GTP-Rac Translocation to the Plasma Membrane Mol. Biol. Cell, July 1, 2008; 19(7): 3111 - 3123. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Tian, C. Pate, A. Andreolotti, L. Wang, E. Tuomanen, K. Boyd, E. Claro, and S. Jackowski Cytokine secretion requires phosphatidylcholine synthesis J. Cell Biol., June 16, 2008; 181(6): 945 - 957. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. L. Herrmann, R. S. Agrawal, S. F. Connolly, R. L. McCaffrey, J. Schlomann, and D. J. Kusner MHC Class II levels and intracellular localization in human dendritic cells are regulated by calmodulin kinase II J. Leukoc. Biol., September 1, 2007; 82(3): 686 - 699. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Kusner, C. R. Thompson, N. A. Melrose, S. M. Pitson, L. M. Obeid, and S. S. Iyer The Localization and Activity of Sphingosine Kinase 1 Are Coordinately Regulated with Actin Cytoskeletal Dynamics in Macrophages J. Biol. Chem., August 10, 2007; 282(32): 23147 - 23162. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Gomez-Cambronero, M. Di Fulvio, and K. Knapek Understanding phospholipase D (PLD) using leukocytes: PLD involvement in cell adhesion and chemotaxis J. Leukoc. Biol., August 1, 2007; 82(2): 272 - 281. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Lehman, M. Di Fulvio, N. McCray, I. Campos, F. Tabatabaian, and J. Gomez-Cambronero Phagocyte cell migration is mediated by phospholipases PLD1 and PLD2 Blood, November 15, 2006; 108(10): 3564 - 3572. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Austin, A. M. Floden, E. J. Murphy, and C. K. Combs {alpha}-Synuclein Expression Modulates Microglial Activation Phenotype J. Neurosci., October 11, 2006; 26(41): 10558 - 10563. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. R. Mazie, J. K. Spix, E. R. Block, H. B. Achebe, and J. K. Klarlund Epithelial cell motility is triggered by activation of the EGF receptor through phosphatidic acid signaling J. Cell Sci., April 15, 2006; 119(8): 1645 - 1654. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S. Iyer, R. S. Agrawal, C. R. Thompson, S. Thompson, J. A. Barton, and D. J. Kusner Phospholipase D1 Regulates Phagocyte Adhesion J. Immunol., March 15, 2006; 176(6): 3686 - 3696. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A. Ivakine, O. M. Gulban, S. M. Mortin-Toth, E. Wankiewicz, C. Scott, D. Spurrell, A. Canty, and J. S. Danska Molecular genetic analysis of the idd4 locus implicates the IFN response in type 1 diabetes susceptibility in nonobese diabetic mice. J. Immunol., March 1, 2006; 176(5): 2976 - 2990. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Cheeseman, T. Ueyama, T. M. Michaud, K. Kashiwagi, D. Wang, L. A. Flax, Y. Shirai, D. J. Loegering, N. Saito, and M. R. Lennartz Targeting of Protein Kinase C-{epsilon} during Fc{gamma} Receptor-dependent Phagocytosis Requires the {epsilon}C1B Domain and Phospholipase C-{gamma}1 Mol. Biol. Cell, February 1, 2006; 17(2): 799 - 813. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Padron, R. D. Tall, and M. G. Roth Phospholipase D2 Is Required for Efficient Endocytic Recycling of Transferrin Receptors Mol. Biol. Cell, February 1, 2006; 17(2): 598 - 606. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. A. Jovanovic, F. D. Brown, and J. G. Donaldson An Effector Domain Mutant of Arf6 Implicates Phospholipase D in Endosomal Membrane Recycling Mol. Biol. Cell, January 1, 2006; 17(1): 327 - 335. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Sukumaran, J. A. Carlyon, J.-L. Cai, N. Berliner, and E. Fikrig Early Transcriptional Response of Human Neutrophils to Anaplasma phagocytophilum Infection Infect. Immun., December 1, 2005; 73(12): 8089 - 8099. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Ueyama, M. Eto, K. Kami, T. Tatsuno, T. Kobayashi, Y. Shirai, M. R. Lennartz, R. Takeya, H. Sumimoto, and N. Saito Isoform-Specific Membrane Targeting Mechanism of Rac during Fc{gamma}R-Mediated Phagocytosis: Positive Charge-Dependent and Independent Targeting Mechanism of Rac to the Phagosome J. Immunol., August 15, 2005; 175(4): 2381 - 2390. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Kamil, B. K. Tischer, S. Trapp, V. K. Nair, N. Osterrieder, and H.-J. Kung vLIP, a Viral Lipase Homologue, Is a Virulence Factor of Marek's Disease Virus J. Virol., June 1, 2005; 79(11): 6984 - 6996. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-S. Lin, C.-W. Yang, D.-W. Wang, and B. A. Wu-Hsieh Dendritic Cells Cross-Present Exogenous Fungal Antigens to Stimulate a Protective CD8 T Cell Response in Infection by Histoplasma capsulatum J. Immunol., May 15, 2005; 174(10): 6282 - 6291. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Swanson and A. D. Hoppe The coordination of signaling during Fc receptor-mediated phagocytosis J. Leukoc. Biol., December 1, 2004; 76(6): 1093 - 1103. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
