Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Logo for

Science 310 (5753): 1492-1495

Copyright © 2005 by the American Association for the Advancement of Science

A Role for the Phagosome in Cytokine Secretion

Rachael Z. Murray, Jason G. Kay, Daniele G. Sangermani, Jennifer L. Stow*

Abstract: Membrane traffic in activated macrophages is required for two critical events in innate immunity: proinflammatory cytokine secretion and phagocytosis of pathogens. We found a joint trafficking pathway linking both actions, which may economize membrane transport and augment the immune response. Tumor necrosis factor {alpha} (TNF{alpha}) is trafficked from the Golgi to the recycling endosome (RE), where vesicle-associated membrane protein 3 mediates its delivery to the cell surface at the site of phagocytic cup formation. Fusion of the RE at the cup simultaneously allows rapid release of TNF{alpha} and expands the membrane for phagocytosis.

Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072, Australia.

* To whom correspondence should be addressed. E-mail: j.stow{at}imb.uq.edu.au

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Emerging roles of recycling endosomes.
T. Taguchi (2013)
J. Biochem. 153, 505-510
   Abstract »    Full Text »    PDF »
Spleen Tyrosine Kinase (Syk)-dependent Calcium Signals Mediate Efficient CpG-induced Exocytosis of Tumor Necrosis Factor {alpha} (TNF{alpha}) in Innate Immune Cells.
S. Rao, X. Liu, B. D. Freedman, and E. M. Behrens (2013)
J. Biol. Chem. 288, 12448-12458
   Abstract »    Full Text »    PDF »
Synaptotagmin XI Regulates Phagocytosis and Cytokine Secretion in Macrophages.
G. Arango Duque, M. Fukuda, and A. Descoteaux (2013)
J. Immunol. 190, 1737-1745
   Abstract »    Full Text »    PDF »
Microparticles from Mycobacteria-Infected Macrophages Promote Inflammation and Cellular Migration.
S. B. Walters, J. Kieckbusch, G. Nagalingam, A. Swain, S. L. Latham, G. E. R. Grau, W. J. Britton, V. Combes, and B. M. Saunders (2013)
J. Immunol. 190, 669-677
   Abstract »    Full Text »    PDF »
Disruption of Ror{alpha}1 and Cholesterol 25-Hydroxylase Expression Attenuates Phagocytosis in Male Ror{alpha}sg/sg Mice.
Z. K. Tuong, P. Lau, J. C. Yeo, M. A. Pearen, A. A. Wall, A. C. Stanley, J. L. Stow, and G. E. O. Muscat (2013)
Endocrinology 154, 140-149
   Abstract »    Full Text »    PDF »
SNAP-23 regulates phagosome formation and maturation in macrophages.
C. Sakurai, H. Hashimoto, H. Nakanishi, S. Arai, Y. Wada, G.-H. Sun-Wada, I. Wada, and K. Hatsuzawa (2012)
Mol. Biol. Cell 23, 4849-4863
   Abstract »    Full Text »    PDF »
Recycling endosome-dependent and -independent mechanisms for IL-10 secretion in LPS-activated macrophages.
A. C. Stanley, Z. Z. Lieu, A. A. Wall, J. Venturato, T. Khromykh, N. A. Hamilton, P. A. Gleeson, and J. L. Stow (2012)
J. Leukoc. Biol. 92, 1227-1239
   Abstract »    Full Text »    PDF »
Effects of IFN-{gamma} on intracellular trafficking and activity of macrophage NADPH oxidase flavocytochrome b558.
A.-J. Casbon, M. E. Long, K. W. Dunn, L.-A. H. Allen, and M. C. Dinauer (2012)
J. Leukoc. Biol. 92, 869-882
   Abstract »    Full Text »    PDF »
Flightless, secreted through a late endosome/lysosome pathway, binds LPS and dampens cytokine secretion.
N. Lei, L. Franken, N. Ruzehaji, C. Offenhauser, A. J. Cowin, and R. Z. Murray (2012)
J. Cell Sci. 125, 4288-4296
   Abstract »    Full Text »    PDF »
Regulation of integrin endocytic recycling and chemotactic cell migration by syntaxin 6 and VAMP3 interaction.
K. A. Riggs, N. Hasan, D. Humphrey, C. Raleigh, C. Nevitt, D. Corbin, and C. Hu (2012)
J. Cell Sci. 125, 3827-3839
   Abstract »    Full Text »    PDF »
Immune regulation of Rab proteins expression and intracellular transport.
G. Pei, M. Bronietzki, and M. G. Gutierrez (2012)
J. Leukoc. Biol. 92, 41-50
   Abstract »    Full Text »    PDF »
Intracellular phosphatidylserine is essential for retrograde membrane traffic through endosomes.
Y. Uchida, J. Hasegawa, D. Chinnapen, T. Inoue, S. Okazaki, R. Kato, S. Wakatsuki, R. Misaki, M. Koike, Y. Uchiyama, et al. (2011)
PNAS 108, 15846-15851
   Abstract »    Full Text »    PDF »
Exclusion of synaptotagmin V at the phagocytic cup by Leishmania donovani lipophosphoglycan results in decreased promastigote internalization.
A. F. Vinet, S. Jananji, S. J. Turco, M. Fukuda, and A. Descoteaux (2011)
Microbiology 157, 2619-2628
   Abstract »    Full Text »    PDF »
Cytokine release from innate immune cells: association with diverse membrane trafficking pathways.
P. Lacy and J. L. Stow (2011)
Blood 118, 9-18
   Abstract »    Full Text »    PDF »
A Novel Aminosaccharide Compound Blocks Immune Responses by Toll-like Receptors and Nucleotide-binding Domain, Leucine-rich Repeat Proteins.
K.-H. Lee, Y.-J. Liu, A. Biswas, C. Ogawa, and K. S. Kobayashi (2011)
J. Biol. Chem. 286, 5727-5735
   Abstract »    Full Text »    PDF »
Palmitoylated Ras proteins traffic through recycling endosomes to the plasma membrane during exocytosis.
R. Misaki, M. Morimatsu, T. Uemura, S. Waguri, E. Miyoshi, N. Taniguchi, M. Matsuda, and T. Taguchi (2010)
J. Cell Biol. 191, 23-29
   Abstract »    Full Text »    PDF »
Phosphoinositide 3-kinase {delta} regulates membrane fission of Golgi carriers for selective cytokine secretion.
P. C. Low, R. Misaki, K. Schroder, A. C. Stanley, M. J. Sweet, R. D. Teasdale, B. Vanhaesebroeck, F. A. Meunier, T. Taguchi, and J. L. Stow (2010)
J. Cell Biol. 190, 1053-1065
   Abstract »    Full Text »    PDF »
The myotubularin phosphatase MTMR4 regulates sorting from early endosomes.
M. J. Naughtin, D. A. Sheffield, P. Rahman, W. E. Hughes, R. Gurung, J. L. Stow, H. H. Nandurkar, J. M. Dyson, and C. A. Mitchell (2010)
J. Cell Sci. 123, 3071-3083
   Abstract »    Full Text »    PDF »
Pathways for Cytokine Secretion.
A. C. Stanley and P. Lacy (2010)
Physiology 25, 218-229
   Abstract »    Full Text »    PDF »
Studies on the Role of Acid Sphingomyelinase and Ceramide in the Regulation of Tumor Necrosis Factor {alpha} (TNF{alpha})-converting Enzyme Activity and TNF{alpha} Secretion in Macrophages.
K. A. Rozenova, G. M. Deevska, A. A. Karakashian, and M. N. Nikolova-Karakashian (2010)
J. Biol. Chem. 285, 21103-21113
   Abstract »    Full Text »    PDF »
Inhibition of phagocytosis in HIV-1-infected macrophages relies on Nef-dependent alteration of focal delivery of recycling compartments.
J. Mazzolini, F. Herit, J. Bouchet, A. Benmerah, S. Benichou, and F. Niedergang (2010)
Blood 115, 4226-4236
   Abstract »    Full Text »    PDF »
Cytokine Secretion Is Distinct from Secretion of Cytotoxic Granules in NK Cells.
E. Reefman, J. G. Kay, S. M. Wood, C. Offenhauser, D. L. Brown, S. Roy, A. C. Stanley, P. C. Low, A. P. Manderson, and J. L. Stow (2010)
J. Immunol. 184, 4852-4862
   Abstract »    Full Text »    PDF »
Sec22b Is a Negative Regulator of Phagocytosis in Macrophages.
K. Hatsuzawa, H. Hashimoto, H. Hashimoto, S. Arai, T. Tamura, A. Higa-Nishiyama, and I. Wada (2009)
Mol. Biol. Cell 20, 4435-4443
   Abstract »    Full Text »    PDF »
Uncoordinated 119 Protein Controls Trafficking of Lck via the Rab11 Endosome and Is Critical for Immunological Synapse Formation.
M. M. Gorska, Q. Liang, Z. Karim, and R. Alam (2009)
J. Immunol. 183, 1675-1684
   Abstract »    Full Text »    PDF »
Deciphering Signaling Outcomes from a System of Complex Networks.
R. C. Hsueh, M. Natarajan, I. Fraser, B. Pond, J. Liu, S. Mumby, H. Han, L. I. Jiang, M. I. Simon, R. Taussig, et al. (2009)
Science Signaling 2, ra22
   Abstract »    Full Text »    PDF »
Human SCAMP5, a Novel Secretory Carrier Membrane Protein, Facilitates Calcium-Triggered Cytokine Secretion by Interaction with SNARE Machinery.
C. Han, T. Chen, M. Yang, N. Li, H. Liu, and X. Cao (2009)
J. Immunol. 182, 2986-2996
   Abstract »    Full Text »    PDF »
RAB13 Participates in Ectoplasmic Specialization Dynamics in the Rat Testis.
D. D. Mruk and A. S.N. Lau (2009)
Biol Reprod 80, 590-601
   Abstract »    Full Text »    PDF »
Macrophage NADPH Oxidase Flavocytochrome b Localizes to the Plasma Membrane and Rab11-Positive Recycling Endosomes.
A.-J. Casbon, L.-A. H. Allen, K. W. Dunn, and M. C. Dinauer (2009)
J. Immunol. 182, 2325-2339
   Abstract »    Full Text »    PDF »
Monomeric IgG Is Neuroprotective via Enhancing Microglial Recycling Endocytosis and TNF-{alpha}.
R. E. Hulse, W. G. Swenson, P. E. Kunkler, D. M. White, and R. P. Kraig (2008)
J. Neurosci. 28, 12199-12211
   Abstract »    Full Text »    PDF »
Regulation of the Endosomal SNARE Protein Syntaxin 7 by Colony-Stimulating Factor 1 in Macrophages.
A. Achuthan, P. Masendycz, J. A. Lopez, T. Nguyen, D. E. James, M. J. Sweet, J. A. Hamilton, and G. M. Scholz (2008)
Mol. Cell. Biol. 28, 6149-6159
   Abstract »    Full Text »    PDF »
The Exocytosis Regulator Synaptotagmin V Controls Phagocytosis in Macrophages.
A. F. Vinet, M. Fukuda, and A. Descoteaux (2008)
J. Immunol. 181, 5289-5295
   Abstract »    Full Text »    PDF »
Splenic nerve is required for cholinergic antiinflammatory pathway control of TNF in endotoxemia.
M. Rosas-Ballina, M. Ochani, W. R. Parrish, K. Ochani, Y. T. Harris, J. M. Huston, S. Chavan, and K. J. Tracey (2008)
PNAS 105, 11008-11013
   Abstract »    Full Text »    PDF »
How a Cytokine Is Chaperoned through the Secretory Pathway by Complexing with Its Own Receptor: Lessons from Interleukin-15 (IL-15)/IL-15 Receptor {alpha}.
E. H. Duitman, Z. Orinska, E. Bulanova, R. Paus, and S. Bulfone-Paus (2008)
Mol. Cell. Biol. 28, 4851-4861
   Abstract »    Full Text »    PDF »
Active Rab11 and functional recycling endosome are required for E-cadherin trafficking and lumen formation during epithelial morphogenesis.
M. Desclozeaux, J. Venturato, F. G. Wylie, J. G. Kay, S. R. Joseph, H. T. Le, and J. L. Stow (2008)
Am J Physiol Cell Physiol 295, C545-C556
   Abstract »    Full Text »    PDF »
The COOH terminus of megalin regulates gene expression in opossum kidney proximal tubule cells.
Y. Li, R. Cong, and D. Biemesderfer (2008)
Am J Physiol Cell Physiol 295, C529-C537
   Abstract »    Full Text »    PDF »
Cathepsin B Is Involved in the Trafficking of TNF-{alpha}-Containing Vesicles to the Plasma Membrane in Macrophages.
S.-D. Ha, A. Martins, K. Khazaie, J. Han, B. M. C. Chan, and S. O. Kim (2008)
J. Immunol. 181, 690-697
   Abstract »    Full Text »    PDF »
The Macrophage-Inducible C-Type Lectin, Mincle, Is an Essential Component of the Innate Immune Response to Candida albicans.
C. A. Wells, J. A. Salvage-Jones, X. Li, K. Hitchens, S. Butcher, R. Z. Murray, A. G. Beckhouse, Y.-L.-S. Lo, S. Manzanero, C. Cobbold, et al. (2008)
J. Immunol. 180, 7404-7413
   Abstract »    Full Text »    PDF »
VAMP-8 segregates mast cell-preformed mediator exocytosis from cytokine trafficking pathways.
N. Tiwari, C.-C. Wang, C. Brochetta, G. Ke, F. Vita, Z. Qi, J. Rivera, M. R. Soranzo, G. Zabucchi, W. Hong, et al. (2008)
Blood 111, 3665-3674
   Abstract »    Full Text »    PDF »
A trans-Golgi network golgin is required for the regulated secretion of TNF in activated macrophages in vivo.
Z. Z. Lieu, J. G. Lock, L. A. Hammond, N. L. La Gruta, J. L. Stow, and P. A. Gleeson (2008)
PNAS 105, 3351-3356
   Abstract »    Full Text »    PDF »
TPL2-mediated activation of ERK1 and ERK2 regulates the processing of pre-TNF{alpha} in LPS-stimulated macrophages.
S. Rousseau, M. Papoutsopoulou, A. Symons, D. Cook, J. M. Lucocq, A. R. Prescott, A. O'Garra, S. C. Ley, and P. Cohen (2008)
J. Cell Sci. 121, 149-154
   Abstract »    Full Text »    PDF »
Phagocytosis of Borrelia burgdorferi, the Lyme Disease Spirochete, Potentiates Innate Immune Activation and Induces Apoptosis in Human Monocytes.
A. R. Cruz, M. W. Moore, C. J. La Vake, C. H. Eggers, J. C. Salazar, and J. D. Radolf (2008)
Infect. Immun. 76, 56-70
   Abstract »    Full Text »    PDF »
Regulation of Fc{gamma}R-stimulated phagocytosis by the 72-kDa inositol polyphosphate 5-phosphatase: SHIP1, but not the 72-kDa 5-phosphatase, regulates complement receptor 3-mediated phagocytosis by differential recruitment of these 5-phosphatases to the phagocytic cup.
K. A. Horan, K.-i. Watanabe, A. M. Kong, C. G. Bailey, J. E. J. Rasko, T. Sasaki, and C. A. Mitchell (2007)
Blood 110, 4480-4491
   Abstract »    Full Text »    PDF »
Fusion, Fission, and Secretion During Phagocytosis.
K. K. Huynh, J. G. Kay, J. L. Stow, and S. Grinstein (2007)
Physiology 22, 366-372
   Abstract »    Full Text »    PDF »
AP-1 and ARF1 Control Endosomal Dynamics at Sites of FcR mediated Phagocytosis.
V. Braun, C. Deschamps, G. Raposo, P. Benaroch, A. Benmerah, P. Chavrier, and F. Niedergang (2007)
Mol. Biol. Cell 18, 4921-4931
   Abstract »    Full Text »    PDF »
Hypoxia causes an increase in phagocytosis by macrophages in a HIF-1{alpha}-dependent manner.
R. J. Anand, S. C. Gribar, J. Li, J. W. Kohler, M. F. Branca, T. Dubowski, C. P. Sodhi, and D. J. Hackam (2007)
J. Leukoc. Biol. 82, 1257-1265
   Abstract »    Full Text »    PDF »
Subcompartments of the macrophage recycling endosome direct the differential secretion of IL-6 and TNF{alpha}.
A. P. Manderson, J. G. Kay, L. A. Hammond, D. L. Brown, and J. L. Stow (2007)
J. Cell Biol. 178, 57-69
   Abstract »    Full Text »    PDF »
Secretion of Apolipoprotein E From Macrophages Occurs via a Protein Kinase A and Calcium-Dependent Pathway Along the Microtubule Network.
M. Kockx, D. L. Guo, T. Huby, P. Lesnik, J. Kay, T. Sabaretnam, E. Jary, M. Hill, K. Gaus, J. Chapman, et al. (2007)
Circ. Res. 101, 607-616
   Abstract »    Full Text »    PDF »
Quantitative Analysis of Membrane Remodeling at the Phagocytic Cup.
W. L. Lee, D. Mason, A. D. Schreiber, and S. Grinstein (2007)
Mol. Biol. Cell 18, 2883-2892
   Abstract »    Full Text »    PDF »
Modulation of Adherence, Invasion, and Tumor Necrosis Factor Alpha Secretion during the Early Stages of Infection by Streptococcus pneumoniae ClpL.
L. N. Tu, H.-Y. Jeong, H.-Y. Kwon, A. D. Ogunniyi, J. C. Paton, S.-N. Pyo, and D.-K. Rhee (2007)
Infect. Immun. 75, 2996-3005
   Abstract »    Full Text »    PDF »
Gpnmb Is Induced in Macrophages by IFN-{gamma} and Lipopolysaccharide and Acts as a Feedback Regulator of Proinflammatory Responses.
V. M. Ripoll, K. M. Irvine, T. Ravasi, M. J. Sweet, and D. A. Hume (2007)
J. Immunol. 178, 6557-6566
   Abstract »    Full Text »    PDF »
Endosomal recycling controls plasma membrane area during mitosis.
E. Boucrot and T. Kirchhausen (2007)
PNAS 104, 7939-7944
   Abstract »    Full Text »    PDF »
Functional Symmetry of Endomembranes.
J. Saraste and B. Goud (2007)
Mol. Biol. Cell 18, 1430-1436
   Abstract »    Full Text »    PDF »
Histone deacetylase inhibitors prevent exocytosis of interleukin-1beta-containing secretory lysosomes: role of microtubules.
S. Carta, S. Tassi, C. Semino, G. Fossati, P. Mascagni, C. A. Dinarello, and A. Rubartelli (2006)
Blood 108, 1618-1626
   Abstract »    Full Text »    PDF »
Regulating secretory lysosomes..
O. J. Holt, F. Gallo, and G. M. Griffiths (2006)
J. Biochem. 140, 7-12
   Abstract »    Full Text »    PDF »
Recycling endosomes.
S. C. D. van IJzendoorn (2006)
J. Cell Sci. 119, 1679-1681
   Full Text »    PDF »
Cytokine Secretion via Cholesterol-rich Lipid Raft-associated SNAREs at the Phagocytic Cup.
J. G. Kay, R. Z. Murray, J. K. Pagan, and J. L. Stow (2006)
J. Biol. Chem. 281, 11949-11954
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882