Tissue macrophages act as cellular chaperones for vascular anastomosis downstream of VEGF-mediated endothelial tip cell induction
Tóm tắt
Blood vessel networks expand in a 2-step process that begins with vessel sprouting and is followed by vessel anastomosis. Vessel sprouting is induced by chemotactic gradients of the vascular endothelial growth factor (VEGF), which stimulates tip cell protrusion. Yet it is not known which factors promote the fusion of neighboring tip cells to add new circuits to the existing vessel network. By combining the analysis of mouse mutants defective in macrophage development or VEGF signaling with live imaging in zebrafish, we now show that macrophages promote tip cell fusion downstream of VEGF-mediated tip cell induction. Macrophages therefore play a hitherto unidentified and unexpected role as vascular fusion cells. Moreover, we show that there are striking molecular similarities between the pro-angiogenic tissue macrophages essential for vascular development and those that promote the angiogenic switch in cancer, including the expression of the cell-surface proteins TIE2 and NRP1. Our findings suggest that tissue macrophages are a target for antiangiogenic therapies, but that they could equally well be exploited to stimulate tissue vascularization in ischemic disease.
Tài liệu tham khảo
Ruhrberg, 2002, Spatially restricted patterning cues provided by heparin-binding VEGF-A control blood vessel branching morphogenesis., Genes Dev, 16, 2684, 10.1101/gad.242002
Gerhardt, 2003, VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia., J Cell Biol, 161, 1163, 10.1083/jcb.200302047
Affolter, 2009, Tissue remodelling through branching morphogenesis., Nat Rev Mol Cell Biol, 10, 831, 10.1038/nrm2797
Grunewald, 2006, VEGF-induced adult neovascularization: recruitment, retention, and role of accessory cells., Cell, 124, 175, 10.1016/j.cell.2005.10.036
Pollard, 2004, Tumour-educated macrophages promote tumour progression and metastasis., Nat Rev Cancer, 4, 71, 10.1038/nrc1256
Lin, 2007, Tumor-associated macrophages press the angiogenic switch in breast cancer., Cancer Res, 67, 5064, 10.1158/0008-5472.CAN-07-0912
Luttun, 2002, Revascularization of ischemic tissues by PlGF treatment, and inhibition of tumor angiogenesis, arthritis and atherosclerosis by anti-Flt1., Nat Med, 8, 831, 10.1038/nm731
Pipp, 2003, VEGFR-1-selective VEGF homologue PlGF is arteriogenic: evidence for a monocyte-mediated mechanism., Circ Res, 92, 378, 10.1161/01.RES.0000057997.77714.72
Kubota, 2009, M-CSF inhibition selectively targets pathological angiogenesis and lymphangiogenesis., J Exp Med, 206, 1089, 10.1084/jem.20081605
Checchin, 2006, Potential role of microglia in retinal blood vessel formation., Invest Ophthalmol Vis Sci, 47, 3595, 10.1167/iovs.05-1522
Espinosa-Heidmann, 2003, Macrophage depletion diminishes lesion size and severity in experimental choroidal neovascularization., Invest Ophthalmol Vis Sci, 44, 3586, 10.1167/iovs.03-0038
Sakurai, 2003, Macrophage depletion inhibits experimental choroidal neovascularization., Invest Ophthalmol Vis Sci, 44, 3578, 10.1167/iovs.03-0097
Pucci, 2009, A distinguishing gene signature shared by tumor-infiltrating Tie2-expressing monocytes (TEMs), blood “resident” monocytes and embryonic macrophages suggests common functions and developmental relationships., Blood, 114, 901, 10.1182/blood-2009-01-200931
Sato, 1995, Distinct roles of the receptor tyrosine kinases Tie-1 and Tie-2 in blood vessel formation., Nature, 376, 70, 10.1038/376070a0
Fantin, 2009, Neuropilin ligands in vascular and neuronal patterning., Biochem Soc Trans, 37, 1228, 10.1042/BST0371228
McKercher, 1996, Targeted disruption of the PU. 1 gene results in multiple hematopoietic abnormalities., EMBO J, 15, 5647, 10.1002/j.1460-2075.1996.tb00949.x
Wiktor-Jedrzejczak, 1990, Total absence of colony-stimulating factor 1 in the macrophage-deficient osteopetrotic (op/op) mouse., Proc Natl Acad Sci U S A, 87, 4828, 10.1073/pnas.87.12.4828
Yoshida, 1990, The murine mutation osteopetrosis is in the coding region of the macrophage colony stimulating factor gene., Nature, 345, 442, 10.1038/345442a0
Gerber, 1999, VEGF is required for growth and survival in neonatal mice., Development, 126, 1149, 10.1242/dev.126.6.1149
Clausen, 1999, Conditional gene targeting in macrophages and granulocytes using LysMcre mice., Transgenic Res, 8, 265, 10.1023/A:1008942828960
Petersen, 2002, Progenitor cell maintenance requires numb and numblike during mouse neurogenesis., Nature, 419, 929, 10.1038/nature01124
Srinivas, 2001, Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus., BMC Dev Biol, 1, 4, 10.1186/1471-213X-1-4
Ivanova, 2005, In vivo genetic ablation by Cre-mediated expression of diphtheria toxin fragment A., Genesis, 43, 129, 10.1002/gene.20162
Peri, 2008, Live imaging of neuronal degradation by microglia reveals a role for v0-ATPase a1 in phagosomal fusion in vivo., Cell, 133, 916, 10.1016/j.cell.2008.04.037
Lawson, 2002, In vivo imaging of embryonic vascular development using transgenic zebrafish., Dev Biol, 248, 307, 10.1006/dbio.2002.0711
Peirson, 2003, Experimental validation of novel and conventional approaches to quantitative real-time PCR data analysis., Nucleic Acids Res, 31, e73, 10.1093/nar/gng073
Herbomel, 1999, Ontogeny and behaviour of early macrophages in the zebrafish embryo., Development, 126, 3735, 10.1242/dev.126.17.3735
Lichanska, 2000, Origins and functions of phagocytes in the embryo., Exp Hematol, 28, 601, 10.1016/S0301-472X(00)00157-0
Sorokin, 1992, Macrophage development: II. Early ontogeny of macrophage populations in brain, liver, and lungs of rat embryos as revealed by a lectin marker., Anat Rec, 232, 527, 10.1002/ar.1092320410
Cuadros, 1993, First appearance, distribution, and origin of macrophages in the early development of the avian central nervous system., J Comp Neurol, 330, 113, 10.1002/cne.903300110
Kurz, 1998, Embryonic CNS macrophages and microglia do not stem from circulating, but from extravascular precursors., Glia, 22, 98, 10.1002/(SICI)1098-1136(199801)22:1<98::AID-GLIA10>3.0.CO;2-V
Austyn, 1981, F4/80, a monoclonal antibody directed specifically against the mouse macrophage., Eur J Immunol, 11, 805, 10.1002/eji.1830111013
Imai, 1996, A novel gene iba1 in the major histocompatibility complex class III region encoding an EF hand protein expressed in a monocytic lineage., Biochem Biophys Res Commun, 224, 855, 10.1006/bbrc.1996.1112
Simon, 1998, PU. 1 and hematopoiesis: lessons learned from gene targeting experiments., Semin Immunol, 10, 111, 10.1006/smim.1998.0112
Scott, 1994, Requirement of transcription factor PU. 1 in the development of multiple hematopoietic lineages., Science, 265, 1573, 10.1126/science.8079170
Lichanska, 1999, Differentiation of the mononuclear phagocyte system during mouse embryogenesis: the role of transcription factor PU. 1., Blood, 94, 127, 10.1182/blood.V94.1.127.413k07_127_138
Olson, 1995, PU. 1 is not essential for early myeloid gene expression but is required for terminal myeloid differentiation., Immunity, 3, 703, 10.1016/1074-7613(95)90060-8
Chang, 1995, Osteopetrotic (op/op) mice deficient in macrophages have the ability to mount a normal T-cell-dependent immune response., Cell Immunol, 162, 146, 10.1006/cimm.1995.1062
Webb, 1996, Direct observation and quantification of macrophage chemoattraction to the growth factor CSF-1., J Cell Sci, 109, 793, 10.1242/jcs.109.4.793
Barleon, 1996, Migration of human monocytes in response to vascular endothelial growth factor (VEGF) is mediated via the VEGF receptor flt-1., Blood, 87, 3336, 10.1182/blood.V87.8.3336.bloodjournal8783336
Haigh, 2003, Cortical and retinal defects caused by dosage-dependent reductions in VEGF-A paracrine signaling., Dev Biol, 262, 225, 10.1016/S0012-1606(03)00356-7
Raab, 2004, Impaired brain angiogenesis and neuronal apoptosis induced by conditional homozygous inactivation of vascular endothelial growth factor., Thromb Haemost, 91, 595, 10.1160/TH03-09-0582
Miquerol, 1999, Multiple developmental roles of VEGF suggested by a LacZ-tagged allele., Dev Biol, 212, 307, 10.1006/dbio.1999.9355
Hiratsuka, 2001, Involvement of Flt-1 tyrosine kinase (vascular endothelial growth factor receptor-1) in pathological angiogenesis., Cancer Res, 61, 1207
Connolly, 1988, Characterization of vascular development in the mouse retina., Microvasc Res, 36, 275, 10.1016/0026-2862(88)90028-3
Rao, 2007, Obligatory participation of macrophages in an angiopoietin 2-mediated cell death switch., Development, 134, 4449, 10.1242/dev.012187
Isogai, 2003, Angiogenic network formation in the developing vertebrate trunk., Development, 130, 5281, 10.1242/dev.00733
Herbomel, 2001, Zebrafish early macrophages colonize cephalic mesenchyme and developing brain, retina, and epidermis through a M-CSF receptor-dependent invasive process., Dev Biol, 238, 274, 10.1006/dbio.2001.0393
Chan, 2007, The origin and cell lineage of microglia: new concepts., Brain Res Rev, 53, 344, 10.1016/j.brainresrev.2006.11.002
Bechmann, 2001, Immune surveillance of mouse brain perivascular spaces by blood-borne macrophages., Eur J Neurosci, 14, 1651, 10.1046/j.0953-816x.2001.01793.x
Herbomel, 2005, Imaging early macrophage differentiation, migration, and behaviors in live zebrafish embryos., Methods Mol Med, 105, 199
Wood, 2000, Mesenchymal cells engulf and clear apoptotic footplate cells in macrophageless PU. 1 null mouse embryos., Development, 127, 5245, 10.1242/dev.127.24.5245
Stockmann, 2008, Deletion of vascular endothelial growth factor in myeloid cells accelerates tumorigenesis., Nature, 456, 814, 10.1038/nature07445
Millard, 2008, Dynamic analysis of filopodial interactions during the zippering phase of Drosophila dorsal closure., Development, 135, 621, 10.1242/dev.014001