经典及替代途径激活巨噬细胞在视网膜新生血管中的作用_Chinese Journal of Ocular Fundus Diseases

Authors：

朱艳吉 , 沈玺 , 钟一声 ,  谢冰

200025 上海交通大学医学院附属瑞金医院眼科;

Corresponding author：

谢冰, Email: brinkleybing@126.com

Keywords：

视网膜新生血管化/病因学; 巨噬细胞; 综述

DOI：

10.3760/cma.j.issn.1005-1015.2014.05.029

Video：

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巨噬细胞(Mf)是非特异性免疫反应的主要效应细胞,分为经典途径激活Mf(M1型)和替代途径激活Mf(M2型)。Mf通过表达细胞外因子蛋白调控血管生成、融合尖端细胞协助血管网形成、改变细胞外基质成分协助血管网构建,从而参与新生血管的形成过程。视网膜新生血管是缺血、缺氧性视网膜病变共有的病理改变,其形成过程涉及到多种细胞因子和调节机制。Mf通过联络和(或)上调各促血管形成因子,发挥促血管生成的作用;Mf激活和极化与新生血管形成过程中的多种分子和细胞功能变化紧密相关。针对Mf的作用机制以及型别调控药物的深入探究,将为视网膜新生血管疾病的治疗寻找到更多的治疗靶点并开发出新型治疗手段。

Citation： 朱艳吉, 沈玺, 钟一声, 谢冰. 经典及替代途径激活巨噬细胞在视网膜新生血管中的作用. Chinese Journal of Ocular Fundus Diseases, 2014, 30(5): 528-531. doi: 10.3760/cma.j.issn.1005-1015.2014.05.029 Copy

1.	Brown DM, Kaiser PK, Michels M, et al. Ranibizumab versus verteporfin for neovascular age-related macular degeneration[J]. N Engl J Med, 2006, 355:1432-1444.
2.	Sica A, Schioppa T, Mantovani A,et al. Tumour-associated marophages are a distinct M2 polarised population promoting tumour progression:potential targets of anti-cancer therapy[J]. Eur J Cancer, 2006, 42:717-727.
3.	Hao NB, Lü MH, Fan YH, et al. Macrophages in tumor microenvironments and the progression of tumors[J/OL]. Clin Dev Immunol, 2012, 2014:948098[2012-01-19]. http://www.hindawi.com/journals/jir/2012/948098/.
4.	Gordon S. Alternative activation of macrophages[J]. Nat Rev Immunol, 2003, 3:23-35.
5.	Stout RD, Watkins SK, Suttles J. Functional plasticity of macrophages:in situ reprogramming of tumor-associated macrophages[J]. J Leukoc Biol, 2009, 86:1105-1109.
6.	Martinez FO, Sica A, Mantovani A, et al. Macrophage activation and polarization[J]. Front Biosci, 2008, 13:453-461.
7.	Cassol E, Cassetta L, Alfano M, et al. Macrophage polarization and HIV-1 infection[J]. J Leukoc Biol, 2010, 87:599-608.
8.	Verreck FA, Boer T, Langenberg DM, et al. Human IL-23-producing type 1 macrophages promote but IL-10-producing type 2 macrophages subvert immunity to (myco)bacteria[J]. Proc Natl Acad Sci USA, 2004, 30, 101:4560-4565.
9.	Kolls JK, Lindén A. Interleukin-17 family members and inflammation[J]. Immunity, 2004, 21:467-476.
10.	Mantovani A, Sica A, Allavena P, et al.Tumor-associated macrophages and the relatedmyeloid-derived suppressor cells as a paradigm of the diversity of macrophage activation[J]. Hum Immunol, 2009, 70:325-330.
11.	Odegaard JI, Chawla A. Mechanisms of macrophage activation in obesity-induced insulin resistance[J]. Nat Clin Pract Endocrinol Metab, 2008, 4:619-626.
12.	Cao X, Shen D, Patel MM, et al. Macrophage polarization in the maculae of age-related macular degeneration:a pilot study[J]. Pathol Int, 2011, 61:528-535.
13.	Sica A, Larghi P, Mancino A, et al. Macrophage polarization in tumour progression[J]. Semin Cancer Biol, 2008, 18:349-355.
14.	Suganami T, Ogawa Y. Adipose tissue macrophages:their role in adipose tissue remodeling[J]. J Leukoc Biol, 2010, 88:33-39.
15.	Mosser DM, Edwards JP. Exploring the full spectrum of macrophage activation[J]. Nat Rev Immunol, 2008, 8:958-969.
16.	Heikkila M, Pasanen A, Kivirikko KI, et al. Roles of the human hypoxia-inducible factor(HIF)-3alpha variants in the hypoxia response[J]. Cell Mol Life Sci, 2011, 68:3885-3901.
17.	Coffelt SB, Hughes R, Lewis CE. Tumor-associated macrophages:effectors of angiogenesis and tumor progression[J]. Biochim Biophys Acta, 2009, 1796:11-18.
18.	Werno C, Menrad H, Weigert A, et al. Knockout of HIF-1alpha in tumor-associated macrophages enhances M2 polarization and attenuates their pro-angiogenic responses[J]. Carcinogenesis, 2010, 31:1863-1872.
19.	Takeda N, O'Dea EL, Doedens A, et al. Differential activation and antagonistic function of HIF-alpha isoforms in macrophages are essential for NO homeostasis[J]. Genes Dev, 2010, 24:491-501.
20.	Sica A, Saccani A, Mantovani A. Tumor-associated macrophages:a molecular perspective[J]. Int Immunopharmacol, 2002, 2:1045-1054.
21.	Patel SA, Simon MC. Biology of hypoxia-induciblefactor- 2alpha in development and disease[J]. Cell Death Differ, 2008, 15:628-634.
22.	Guruvayoorappan C.Tumor versus tumor-associated macrophages:how hot is the link?[J]. Integr Cancer Ther, 2008, 7:90-95.
23.	Pucci F, Venneri MA, Biziato D, et al. A distinguishing gene signature shared by tumor-infiltrating Tie2-expressing monocytes, blood "resident" monocytes, and embryonic macrophages suggests common functions and developmental relationships[J], Blood, 2009, 114:901-914.
24.	Coffelt SB, Tal AO, Scholz A, et al. Angiopoietin-2 regulates gene expression in Tie2-expressing monocytes and augments their inherent proangiogenic functions[J]. Cancer Res, 2010, 70:5270-5280.
25.	Biswas SK, Lewis CE. NF-kappaB as a central regulator of macrophage function in tumors[J]. J Leukoc Biol, 2010, 88:877-884.
26.	Ma J, Mehta M, Lam G, et al. Influence of subretinal fluid in advanced stage retinopathy of prematurity on proangiogenic response and cell proliferation[J]. Mol Vis, 2014, 20:881-893.
27.	Rijsewijk F, Schuermann M, Wagenaar E, et al. Thedrosophila homolog of the mouse mammary oncogene int-1 is identical to the segment polarity gene wingless[J]. Cell, 1987, 50:649-667.
28.	Wu J, Cohen SM. Repression of Teashirt marks the initiation of wing development[J]. Development, 2002, 129:2411-2418.
29.	Nusse R, van Ooyen A, Cox D, et al. Mode of proviral activation of a putative mammary oncogene (int-1) on mouse chromosome 15[J]. Nature, 1984, 307:131-136.
30.	Fan Y, Ye J, Shen F, et al. Interleukin-6 stimulates circulating bloodderived endothelial progenitor cell angiogenesis in vitro[J].J Cereb Blood Flow Metab, 2008, 28:90-98.
31.	Rosell A, Arai K, Lok J, et al. Interleukin-1beta augments angiogenic responses of murine endothelial progenitor cells in vitro[J]. J Cereb Blood Flow Metab, 2009, 29:933-943.
32.	Kim J, Kim DW, Ha Y, et al. Wnt5a induces endothelial inflammation via beta-catenin-independent signaling[J]. J Immunol, 2010, 185:1274-1282.
33.	Cheng CW, Yeh JC, Fan TP, et al. Wnt5a-mediated non-canonical Wnt signalling regulates human endothelial cell proliferation and migration[J]. Biochem Biophys Res Commun, 2008, 365:285-290.
34.	Diez-Roux G, Argilla M, Makarenkova H, et al. Macrophages kill capillary cells in G1 phase of the cell cycle during programmed vascular regression[J]. Development, 1999, 126:2141-2147.
35.	Rao S, Lobov IB, Vallance JE, et al.Obligatory participation of macrophages in an angiopoietin 2-mediated cell death switch[J]. Development, 2007, 134:4449-4458.
36.	Stefater JA, Lewkowich I, Rao S, et al. Regulation of angiogenesis by anon-canonical Wnt-Flt1 pathway in myeloid cells[J]. Nature, 2011, 474:511-515.
37.	Fantin A, Vieira JM, Gestri G, et al.Tissue macrophages act as cellular chaperones for vascular anastomosis downstream of VEGF-mediated endothelial tip cell induction[J]. Blood, 2010, 116:829-840.
38.	Ingber DE. Extracellular matrix as a solid-state regulator in angiogenesis:identification of new targets for anti-cancer therapy[J]. Semin Cancer Biol, 1992, 3:57-63.
39.	Schulze-Osthoff K, Risau W, Vollmer E, et al. In situ detection of basic fibroblast growth factor by highly specific antibodies[J].Am J Pathol, 1990, 137:85-92.
40.	Berse B, Brown LF, van de Water L, et al. Vascular permeability factor (vascular endothelial growth factor) gene is expressed differentially in normal tissues, macrophages, and tumors[J]. Mol Biol Cell, 1992, 3:211-220.
41.	Schioppa T, Uranchimeg B, Saccani A, et al. Regulation of the chemokine receptor CXCR4 by hypoxia[J]. J Exp Med, 2003, 198:1391-1402.
42.	Schoppmann SF, Birner P, St ckl J, et al. Tumor-associated macrophages express lymphatic endothelial growth factors and are related to peritumoral lymphangiogenesis[J]. Am J Pathol, 2002, 161:947-956.
43.	Tseng D, Vasquez-Medrano DA, Brown JM. Targeting SDF-1/CXCR4 to inhibit tumour vasculature for treatment of glioblastomas[J]. Br J Cancer, 2011, 104:1805-1809.
44.	Schmid MC, Avraamides CJ, Foubert P, et al. Combined blockade of integrin-α4β1 plus cytokines SDF-1α or IL-1β potently inhibits tumor inflammation and growth[J]. Cancer Res, 2011, 71:6965-6975.
45.	Fischer C, Mazzone M, Jonckx B, et al. FLT1 and its ligands VEGFB and PlGF:drug targets for anti-angiogenic therapy?[J]. Nat Rev Cancer, 2008, 12:942-956.
46.	Zhang W, Zhu XD, Sun HC, et al. Depletion of tumorassociated macrophages enhances the effect of sorafenib in metastatic liver cancer models by antimetastatic and antiangiogenic effects[J]. Clin Cancer Res, 2010, 16:3420-3430.
47.	Dineen SP, Lynn KD, Holloway SE, et al.Vascular endothelial growth factor receptor 2 mediates macrophage infiltration into orthotopic pancreatic tumors in mice[J]. Cancer Res, 2008, 68:4340-4346.
48.	Guiducci C, Vicari AP, Sangaletti S, et al. Redirecting in vivo elicited tumor infiltrating macrophages and dendritic cells towards tumor rejection[J].Cancer Res, 2005, 65:3437-3446.
49.	Rauh MJ, Sly LM, Kalesnikoff J, et al.The role of SHIP1 in macrophage programming and activation. Biochem Soc Trans, 2004, 32:785-788.

1. Brown DM, Kaiser PK, Michels M, et al. Ranibizumab versus verteporfin for neovascular age-related macular degeneration[J]. N Engl J Med, 2006, 355:1432-1444.
2. Sica A, Schioppa T, Mantovani A,et al. Tumour-associated marophages are a distinct M2 polarised population promoting tumour progression:potential targets of anti-cancer therapy[J]. Eur J Cancer, 2006, 42:717-727.
3. Hao NB, Lü MH, Fan YH, et al. Macrophages in tumor microenvironments and the progression of tumors[J/OL]. Clin Dev Immunol, 2012, 2014:948098[2012-01-19]. http://www.hindawi.com/journals/jir/2012/948098/.
4. Gordon S. Alternative activation of macrophages[J]. Nat Rev Immunol, 2003, 3:23-35.
5. Stout RD, Watkins SK, Suttles J. Functional plasticity of macrophages:in situ reprogramming of tumor-associated macrophages[J]. J Leukoc Biol, 2009, 86:1105-1109.
6. Martinez FO, Sica A, Mantovani A, et al. Macrophage activation and polarization[J]. Front Biosci, 2008, 13:453-461.
7. Cassol E, Cassetta L, Alfano M, et al. Macrophage polarization and HIV-1 infection[J]. J Leukoc Biol, 2010, 87:599-608.
8. Verreck FA, Boer T, Langenberg DM, et al. Human IL-23-producing type 1 macrophages promote but IL-10-producing type 2 macrophages subvert immunity to (myco)bacteria[J]. Proc Natl Acad Sci USA, 2004, 30, 101:4560-4565.
9. Kolls JK, Lindén A. Interleukin-17 family members and inflammation[J]. Immunity, 2004, 21:467-476.
10. Mantovani A, Sica A, Allavena P, et al.Tumor-associated macrophages and the relatedmyeloid-derived suppressor cells as a paradigm of the diversity of macrophage activation[J]. Hum Immunol, 2009, 70:325-330.
11. Odegaard JI, Chawla A. Mechanisms of macrophage activation in obesity-induced insulin resistance[J]. Nat Clin Pract Endocrinol Metab, 2008, 4:619-626.
12. Cao X, Shen D, Patel MM, et al. Macrophage polarization in the maculae of age-related macular degeneration:a pilot study[J]. Pathol Int, 2011, 61:528-535.
13. Sica A, Larghi P, Mancino A, et al. Macrophage polarization in tumour progression[J]. Semin Cancer Biol, 2008, 18:349-355.
14. Suganami T, Ogawa Y. Adipose tissue macrophages:their role in adipose tissue remodeling[J]. J Leukoc Biol, 2010, 88:33-39.
15. Mosser DM, Edwards JP. Exploring the full spectrum of macrophage activation[J]. Nat Rev Immunol, 2008, 8:958-969.
16. Heikkila M, Pasanen A, Kivirikko KI, et al. Roles of the human hypoxia-inducible factor(HIF)-3alpha variants in the hypoxia response[J]. Cell Mol Life Sci, 2011, 68:3885-3901.
17. Coffelt SB, Hughes R, Lewis CE. Tumor-associated macrophages:effectors of angiogenesis and tumor progression[J]. Biochim Biophys Acta, 2009, 1796:11-18.
18. Werno C, Menrad H, Weigert A, et al. Knockout of HIF-1alpha in tumor-associated macrophages enhances M2 polarization and attenuates their pro-angiogenic responses[J]. Carcinogenesis, 2010, 31:1863-1872.
19. Takeda N, O'Dea EL, Doedens A, et al. Differential activation and antagonistic function of HIF-alpha isoforms in macrophages are essential for NO homeostasis[J]. Genes Dev, 2010, 24:491-501.
20. Sica A, Saccani A, Mantovani A. Tumor-associated macrophages:a molecular perspective[J]. Int Immunopharmacol, 2002, 2:1045-1054.
21. Patel SA, Simon MC. Biology of hypoxia-induciblefactor- 2alpha in development and disease[J]. Cell Death Differ, 2008, 15:628-634.
22. Guruvayoorappan C.Tumor versus tumor-associated macrophages:how hot is the link?[J]. Integr Cancer Ther, 2008, 7:90-95.
23. Pucci F, Venneri MA, Biziato D, et al. A distinguishing gene signature shared by tumor-infiltrating Tie2-expressing monocytes, blood "resident" monocytes, and embryonic macrophages suggests common functions and developmental relationships[J], Blood, 2009, 114:901-914.
24. Coffelt SB, Tal AO, Scholz A, et al. Angiopoietin-2 regulates gene expression in Tie2-expressing monocytes and augments their inherent proangiogenic functions[J]. Cancer Res, 2010, 70:5270-5280.
25. Biswas SK, Lewis CE. NF-kappaB as a central regulator of macrophage function in tumors[J]. J Leukoc Biol, 2010, 88:877-884.
26. Ma J, Mehta M, Lam G, et al. Influence of subretinal fluid in advanced stage retinopathy of prematurity on proangiogenic response and cell proliferation[J]. Mol Vis, 2014, 20:881-893.
27. Rijsewijk F, Schuermann M, Wagenaar E, et al. Thedrosophila homolog of the mouse mammary oncogene int-1 is identical to the segment polarity gene wingless[J]. Cell, 1987, 50:649-667.
28. Wu J, Cohen SM. Repression of Teashirt marks the initiation of wing development[J]. Development, 2002, 129:2411-2418.
29. Nusse R, van Ooyen A, Cox D, et al. Mode of proviral activation of a putative mammary oncogene (int-1) on mouse chromosome 15[J]. Nature, 1984, 307:131-136.
30. Fan Y, Ye J, Shen F, et al. Interleukin-6 stimulates circulating bloodderived endothelial progenitor cell angiogenesis in vitro[J].J Cereb Blood Flow Metab, 2008, 28:90-98.
31. Rosell A, Arai K, Lok J, et al. Interleukin-1beta augments angiogenic responses of murine endothelial progenitor cells in vitro[J]. J Cereb Blood Flow Metab, 2009, 29:933-943.
32. Kim J, Kim DW, Ha Y, et al. Wnt5a induces endothelial inflammation via beta-catenin-independent signaling[J]. J Immunol, 2010, 185:1274-1282.
33. Cheng CW, Yeh JC, Fan TP, et al. Wnt5a-mediated non-canonical Wnt signalling regulates human endothelial cell proliferation and migration[J]. Biochem Biophys Res Commun, 2008, 365:285-290.
34. Diez-Roux G, Argilla M, Makarenkova H, et al. Macrophages kill capillary cells in G1 phase of the cell cycle during programmed vascular regression[J]. Development, 1999, 126:2141-2147.
35. Rao S, Lobov IB, Vallance JE, et al.Obligatory participation of macrophages in an angiopoietin 2-mediated cell death switch[J]. Development, 2007, 134:4449-4458.
36. Stefater JA, Lewkowich I, Rao S, et al. Regulation of angiogenesis by anon-canonical Wnt-Flt1 pathway in myeloid cells[J]. Nature, 2011, 474:511-515.
37. Fantin A, Vieira JM, Gestri G, et al.Tissue macrophages act as cellular chaperones for vascular anastomosis downstream of VEGF-mediated endothelial tip cell induction[J]. Blood, 2010, 116:829-840.
38. Ingber DE. Extracellular matrix as a solid-state regulator in angiogenesis:identification of new targets for anti-cancer therapy[J]. Semin Cancer Biol, 1992, 3:57-63.
39. Schulze-Osthoff K, Risau W, Vollmer E, et al. In situ detection of basic fibroblast growth factor by highly specific antibodies[J].Am J Pathol, 1990, 137:85-92.
40. Berse B, Brown LF, van de Water L, et al. Vascular permeability factor (vascular endothelial growth factor) gene is expressed differentially in normal tissues, macrophages, and tumors[J]. Mol Biol Cell, 1992, 3:211-220.
41. Schioppa T, Uranchimeg B, Saccani A, et al. Regulation of the chemokine receptor CXCR4 by hypoxia[J]. J Exp Med, 2003, 198:1391-1402.
42. Schoppmann SF, Birner P, St ckl J, et al. Tumor-associated macrophages express lymphatic endothelial growth factors and are related to peritumoral lymphangiogenesis[J]. Am J Pathol, 2002, 161:947-956.
43. Tseng D, Vasquez-Medrano DA, Brown JM. Targeting SDF-1/CXCR4 to inhibit tumour vasculature for treatment of glioblastomas[J]. Br J Cancer, 2011, 104:1805-1809.
44. Schmid MC, Avraamides CJ, Foubert P, et al. Combined blockade of integrin-α4β1 plus cytokines SDF-1α or IL-1β potently inhibits tumor inflammation and growth[J]. Cancer Res, 2011, 71:6965-6975.
45. Fischer C, Mazzone M, Jonckx B, et al. FLT1 and its ligands VEGFB and PlGF:drug targets for anti-angiogenic therapy?[J]. Nat Rev Cancer, 2008, 12:942-956.
46. Zhang W, Zhu XD, Sun HC, et al. Depletion of tumorassociated macrophages enhances the effect of sorafenib in metastatic liver cancer models by antimetastatic and antiangiogenic effects[J]. Clin Cancer Res, 2010, 16:3420-3430.
47. Dineen SP, Lynn KD, Holloway SE, et al.Vascular endothelial growth factor receptor 2 mediates macrophage infiltration into orthotopic pancreatic tumors in mice[J]. Cancer Res, 2008, 68:4340-4346.
48. Guiducci C, Vicari AP, Sangaletti S, et al. Redirecting in vivo elicited tumor infiltrating macrophages and dendritic cells towards tumor rejection[J].Cancer Res, 2005, 65:3437-3446.
49. Rauh MJ, Sly LM, Kalesnikoff J, et al.The role of SHIP1 in macrophage programming and activation. Biochem Soc Trans, 2004, 32:785-788.

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