Journal of Cell Science, Vol 109, Issue 4 793-803, Copyright © 1996 by Company of Biologists

JOURNAL ARTICLES

Direct observation and quantification of macrophage chemoattraction to the growth factor CSF-1

SE Webb, JW Pollard and GE Jones
Bandall Institute, King's College London, UK.

The cloned mouse macrophage cell line, BAC1.25F, resembles primary macrophages in its dependence on colony stimulating factor-1 (CSF-1) for both viability and proliferation. Re-addition of CSF-1 to cytokine-deprived cells, which are rounded with diffusely organised F-actin, stimulates rapid cell spreading and cell polarisation. Using the Dunn chemotaxis chamber the movement of stimulated macrophages was monitored over a 2 hour period. Cells restimulated with 1.32 nM human recombinant CSF-1 migrated at a mean rate of 7.71 microns per hour, but showed no directional preferences. In a linear concentration gradient of CSF-1, cytokine-deprived cells were again stimulated to migrate and the mean rate of cell motility, at 6.88 microns per hour, was not significantly different from that measured in an isotropic environment of CSF-1. However, there was a strong preference for the cells to orientate so that their long axes aligned with the CSF-1 gradient and they migrated preferentially towards the source of CSF-1. Migrating cells contained abundant F-actin within the leading lamellae as judged by confocal imaging of fluorescent phalloidin, but the actin was not arranged into stress fibre-like structures. These data support the proposition that CSF-1 is both a chemokinetic and chemotactic agent for macrophages. Tumour necrosis factor (TNF-alpha) failed to stimulate cell migration and thus was neither chemokinetic nor a chemotactic agent. However, cells exposed to a dual concentration gradient of both TNF-alpha and CSF-1 did migrate successfully, although the chemotactic response to CSF-1 was abolished.

This article has been cited by other articles:

				W. V. Ingman and R. L. Jones Cytokine knockouts in reproduction: the use of gene ablation to dissect roles of cytokines in reproductive biology Hum. Reprod. Update, March 1, 2008; 14(2): 179 - 192. [Abstract] [Full Text] [PDF]

				W. Abou-Kheir, B. Isaac, H. Yamaguchi, and D. Cox Membrane targeting of WAVE2 is not sufficient for WAVE2-dependent actin polymerization: a role for IRSp53 in mediating the interaction between Rac and WAVE2 J. Cell Sci., February 1, 2008; 121(3): 379 - 390. [Abstract] [Full Text] [PDF]

				K. A. Owen, F. J. Pixley, K. S. Thomas, M. Vicente-Manzanares, B. J. Ray, A. F. Horwitz, J. T. Parsons, H. E. Beggs, E. R. Stanley, and A. H. Bouton Regulation of lamellipodial persistence, adhesion turnover, and motility in macrophages by focal adhesion kinase J. Cell Biol., December 17, 2007; 179(6): 1275 - 1287. [Abstract] [Full Text] [PDF]

				A. Tonello and G. Poli Tubal ectopic pregnancy: macrophages under the microscope Hum. Reprod., October 1, 2007; 22(10): 2577 - 2584. [Abstract] [Full Text] [PDF]

				M. Zaki, N. Andrew, and R. H. Insall Entamoeba histolytica cell movement: A central role for self-generated chemokines and chemorepellents PNAS, December 5, 2006; 103(49): 18751 - 18756. [Abstract] [Full Text] [PDF]

				P. J. Ancliff, M. P. Blundell, G. O. Cory, Y. Calle, A. Worth, H. Kempski, S. Burns, G. E. Jones, J. Sinclair, C. Kinnon, et al. Two novel activating mutations in the Wiskott-Aldrich syndrome protein result in congenital neutropenia Blood, October 1, 2006; 108(7): 2182 - 2189. [Abstract] [Full Text] [PDF]

				M.-H. Jang, D. M. Herber, X. Jiang, S. Nandi, X.-M. Dai, G. Zeller, E. R. Stanley, and V. R. Kelley Distinct In Vivo Roles of Colony-Stimulating Factor-1 Isoforms in Renal Inflammation J. Immunol., September 15, 2006; 177(6): 4055 - 4063. [Abstract] [Full Text] [PDF]

				I. O. Gordon and R. S. Freedman Defective Antitumor Function of Monocyte-Derived Macrophages from Epithelial Ovarian Cancer Patients Clin. Cancer Res., March 1, 2006; 12(5): 1515 - 1524. [Abstract] [Full Text] [PDF]

				S. Blazquez, C. Zimmer, G. Guigon, J.-C. Olivo-Marin, N. Guillen, and E. Labruyere Human Tumor Necrosis Factor is a Chemoattractant for the Parasite Entamoeba histolytica Infect. Immun., February 1, 2006; 74(2): 1407 - 1411. [Abstract] [Full Text] [PDF]

				B. Onfelt, M. A. Purbhoo, S. Nedvetzki, S. Sowinski, and D. M. Davis Long-Distance Calls Between Cells Connected by Tunneling Nanotubules Sci. Signal., December 6, 2005; 2005(313): pe55 - pe55. [Abstract] [Full Text] [PDF]

				W. Abou Kheir, J.-C. Gevrey, H. Yamaguchi, B. Isaac, and D. Cox A WAVE2-Abi1 complex mediates CSF-1-induced F-actin-rich membrane protrusions and migration in macrophages J. Cell Sci., November 15, 2005; 118(22): 5369 - 5379. [Abstract] [Full Text] [PDF]

				V. Chitu, F. J. Pixley, F. Macaluso, D. R. Larson, J. Condeelis, Y.-G. Yeung, and E. R. Stanley The PCH Family Member MAYP/PSTPIP2 Directly Regulates F-Actin Bundling and Enhances Filopodia Formation and Motility in Macrophages Mol. Biol. Cell, June 1, 2005; 16(6): 2947 - 2959. [Abstract] [Full Text] [PDF]

				V. Vedham, H. Phee, and K. M. Coggeshall Vav Activation and Function as a Rac Guanine Nucleotide Exchange Factor in Macrophage Colony-Stimulating Factor-Induced Macrophage Chemotaxis Mol. Cell. Biol., May 15, 2005; 25(10): 4211 - 4220. [Abstract] [Full Text] [PDF]

				F. J. Pixley, Y. Xiong, R. Y.-L. Yu, E. A. Sahai, E. R. Stanley, and B. H. Ye BCL6 suppresses RhoA activity to alter macrophage morphology and motility J. Cell Sci., May 1, 2005; 118(9): 1873 - 1883. [Abstract] [Full Text] [PDF]

				C. Weiss-Haljiti, C. Pasquali, H. Ji, C. Gillieron, C. Chabert, M.-L. Curchod, E. Hirsch, A. J. Ridley, R. H. van Huijsduijnen, M. Camps, et al. Involvement of Phosphoinositide 3-Kinase {gamma}, Rac, and PAK Signaling in Chemokine-induced Macrophage Migration J. Biol. Chem., October 8, 2004; 279(41): 43273 - 43284. [Abstract] [Full Text] [PDF]

				J. Koivunen, V. Aaltonen, S. Koskela, P. Lehenkari, M. Laato, and J. Peltonen Protein Kinase C {alpha}/{beta} Inhibitor Go6976 Promotes Formation of Cell Junctions and Inhibits Invasion of Urinary Bladder Carcinoma Cells Cancer Res., August 15, 2004; 64(16): 5693 - 5701. [Abstract] [Full Text] [PDF]

				S. Aharinejad, P. Paulus, M. Sioud, M. Hofmann, K. Zins, R. Schafer, E. R. Stanley, and D. Abraham Colony-Stimulating Factor-1 Blockade by Antisense Oligonucleotides and Small Interfering RNAs Suppresses Growth of Human Mammary Tumor Xenografts in Mice Cancer Res., August 1, 2004; 64(15): 5378 - 5384. [Abstract] [Full Text] [PDF]

				L. Banaei-Bouchareb, V. Gouon-Evans, D. Samara-Boustani, M. C. Castellotti, P. Czernichow, J. W. Pollard, and M. Polak Insulin cell mass is altered in Csf1op/Csf1op macrophage-deficient mice J. Leukoc. Biol., August 1, 2004; 76(2): 359 - 367. [Abstract] [Full Text] [PDF]

				C. M. Wells, M. Walmsley, S. Ooi, V. Tybulewicz, and A. J. Ridley Rac1-deficient macrophages exhibit defects in cell spreading and membrane ruffling but not migration J. Cell Sci., March 1, 2004; 117(7): 1259 - 1268. [Abstract] [Full Text] [PDF]

				X.-M. Dai, X.-H. Zong, V. Sylvestre, and E. R. Stanley Incomplete restoration of colony-stimulating factor 1 (CSF-1) function in CSF-1-deficient Csf1op/Csf1op mice by transgenic expression of cell surface CSF-1 Blood, February 1, 2004; 103(3): 1114 - 1123. [Abstract] [Full Text] [PDF]

				H. Zhang, L. Vutskits, V. Calaora, P. Durbec, and J. Z. Kiss A role for the polysialic acid - neural cell adhesion molecule in PDGF-induced chemotaxis of oligodendrocyte precursor cells J. Cell Sci., January 1, 2004; 117(1): 93 - 103. [Abstract] [Full Text] [PDF]

				H. Zhang, L. Vutskits, M. S. Pepper, and J. Z. Kiss VEGF is a chemoattractant for FGF-2-stimulated neural progenitors J. Cell Biol., December 22, 2003; 163(6): 1375 - 1384. [Abstract] [Full Text] [PDF]

				R. S.F. Lee, N. Li, A. M. Ledgard, and J. W. Pollard Dynamic Regulation of Expression of Colony-Stimulating Factor 1 in the Reproductive Tract of Cattle During the Estrous Cycle and in Pregnancy Biol Reprod, August 1, 2003; 69(2): 518 - 528. [Abstract] [Full Text] [PDF]

				D. M. Lenda, E. Kikawada, E. R. Stanley, and V. R. Kelley Reduced Macrophage Recruitment, Proliferation, and Activation in Colony-Stimulating Factor-1-Deficient Mice Results in Decreased Tubular Apoptosis During Renal Inflammation J. Immunol., March 15, 2003; 170(6): 3254 - 3262. [Abstract] [Full Text] [PDF]

				J. Sturge, J. Hamelin, and G. E. Jones N-WASP activation by a {beta}1-integrin-dependent mechanism supports PI3K-independent chemotaxis stimulated by urokinase-type plasminogen activator J. Cell Sci., February 15, 2002; 115(4): 699 - 711. [Abstract] [Full Text] [PDF]

				T. Bernier, T. Tschernig, R. Pabst, O. Macke, C. Steinmueller, and A. Emmendorffer Effects of macrophage-CSF on pulmonary-macrophage repopulation after bone marrow transplantation J. Leukoc. Biol., July 1, 2001; 70(1): 39 - 45. [Abstract] [Full Text] [PDF]

				S. Honda, Y. Sasaki, K. Ohsawa, Y. Imai, Y. Nakamura, K. Inoue, and S. Kohsaka Extracellular ATP or ADP Induce Chemotaxis of Cultured Microglia through Gi/o-Coupled P2Y Receptors J. Neurosci., March 15, 2001; 21(6): 1975 - 1982. [Abstract] [Full Text] [PDF]

				I. Guleria and J. W. Pollard Aberrant Macrophage and Neutrophil Population Dynamics and Impaired Th1 Response to Listeria monocytogenes in Colony-Stimulating Factor 1-Deficient Mice Infect. Immun., March 1, 2001; 69(3): 1795 - 1807. [Abstract] [Full Text] [PDF]

				F. J. Pixley, P. S. W. Lee, J. S. Condeelis, and E. R. Stanley Protein Tyrosine Phosphatase {phi} Regulates Paxillin Tyrosine Phosphorylation and Mediates Colony-Stimulating Factor 1-Induced Morphological Changes in Macrophages Mol. Cell. Biol., March 1, 2001; 21(5): 1795 - 1809. [Abstract] [Full Text]

				G. E. Jones Cellular signaling in macrophage migration and chemotaxis J. Leukoc. Biol., November 1, 2000; 68(5): 593 - 602. [Abstract] [Full Text]

				M. Peppelenbosch, E. Boone, G. E. Jones, S.J.H. v. Deventer, G. Haegeman, W. Fiers, J. Grooten, and A. J. Ridley Multiple Signal Transduction Pathways Regulate TNF-Induced Actin Reorganization in Macrophages: Inhibition of Cdc42-Mediated Filopodium Formation by TNF J. Immunol., January 15, 1999; 162(2): 837 - 845. [Abstract] [Full Text] [PDF]

				Y.-G. Yeung, S. Soldera, and E. R. Stanley A Novel Macrophage Actin-associated Protein (MAYP) Is Tyrosine-phosphorylated following Colony Stimulating Factor-1 Stimulation J. Biol. Chem., November 13, 1998; 273(46): 30638 - 30642. [Abstract] [Full Text] [PDF]

				Y.-G. Yeung, Y. Wang, D. B. Einstein, P. S. W. Lee, and E. R. Stanley Colony-stimulating Factor-1 Stimulates the Formation of Multimeric Cytosolic Complexes of Signaling Proteins and Cytoskeletal Components in Macrophages J. Biol. Chem., July 3, 1998; 273(27): 17128 - 17137. [Abstract] [Full Text] [PDF]

				W. E. Allen, D. Zicha, A. J. Ridley, and G. E. Jones A Role for Cdc42 in Macrophage Chemotaxis J. Cell Biol., June 1, 1998; 141(5): 1147 - 1157. [Abstract] [Full Text] [PDF]

				W. Allen, G. Jones, J. Pollard, and A. Ridley Rho, Rac and Cdc42 regulate actin organization and cell adhesion in macrophages J. Cell Sci., January 3, 1997; 110(6): 707 - 720. [Abstract] [PDF]