Macrophages in homeostatic immune function

Frontiers in Physiology

Volumn 5 MAY, Issue , 2014, Pages

  Jantsch, Jonathan ^a   Binger, Katrina J ^b   Müller, Dominik N ^b   Titze, Jens ^c,d  

^a UNIVERSITY HOSPITAL ERLANGEN   (Germany)

^b CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^c UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

^d VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Angiogenesis; Arteriogenesis; Lipid metabolism; Macrophage polarization; Peroxisome proliferator activator receptor (PPAR); Salt; Tonicity enhance binding protein (TonEBP) nuclear factor of activated T cells 5(NFAT5)

Indexed keywords

ANGIOPOIETIN 1; FIBROBLAST GROWTH FACTOR 2; GLUCOSE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 4; LIPID; MEMBRANE PROTEIN; NUCLEAR FACTOR OF ACTIVATED T CELL 5; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR; SODIUM CHLORIDE; STAT6 PROTEIN; TISSUE INHIBITOR OF METALLOPROTEINASE 1; UNCLASSIFIED DRUG; VASCULOTROPIN; VASCULOTROPIN RECEPTOR 3;

ACCESSORY CELL; ANGIOGENESIS; CELL FUNCTION; ELECTROLYTE TRANSPORT; ENZYME ACTIVATION; ENZYME REPRESSION; FLUID BALANCE; HOMEOSTASIS; HUMAN; HYPERTENSION; IMMUNITY; ISCHEMIA; MACROPHAGE; METABOLIC DISORDER; METABOLISM; NONHUMAN; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; SKIN; SODIUM BALANCE;

EID: 84904288394     PISSN: None     EISSN: 1664042X     Source Type: Journal    
DOI: 10.3389/fphys.2014.00146     Document Type: Review

References (102)

1. Arkan, M. C., Hevener, A. L., Greten, F. R., Maeda, S., Li, Z. W., Long, J. M., et al. (2005). IKK-beta links inflammation to obesity-induced insulin resistance. Nat. Med. 11, 191-198. doi: 10.1038/nm1185.
2. Avraham-Davidi, I., Yona, S., Grunewald, M., Landsman, L., Cochain, C., Silvestre, J. S., et al. (2013). On-site education of VEGF-recruited monocytes improves their performance as angiogenic and arteriogenic accessory cells. J. Exp. Med. 210, 2611-2625. doi: 10.1084/jem.20120690.
3. Bernard, C. (1957). An Introduction to the Study of Experimental Medicine. New York, NY: Dover Publications.
4. Brewster, J. L., de Valoir, T., Dwyer, N. D., Winter, E., and Gustin, M. C. (1993). An osmosensing signal transduction pathway in yeast. Science 259, 1760-1763.
5. Byles, V., Covarrubias, A. J., Ben-Sahra, I., Lamming, D. W., Sabatini, D. M., Manning, B. D., et al. (2013). The TSC-mTOR pathway regulates macrophage polarization. Nat. Commun. 4:2834. doi: 10.1038/ncomms3834.
6. Chambers, S. E., O'Neill, C. L., O'Doherty, T. M., Medina, R. J., and Stitt, A. W. (2013). The role of immune-related myeloid cells in angiogenesis. Immunobiology 218, 1370-1375. doi: 10.1016/j.imbio.2013.06.010.
7. Clark, K., MacKenzie, K. F., Petkevicius, K., Kristariyanto, Y., Zhang, J., Choi, H. G., et al. (2012). Phosphorylation of CRTC3 by the salt-inducible kinases controls the interconversion of classically activated and regulatory macrophages. Proc. Natl. Acad. Sci. U.S.A. 109, 16986-16991. doi: 10.1073/pnas.1215450109.
8. Coffelt, S. B., Chen, Y, Muthana, M., Welford, A. F., Tal, A. O., Scholz, A., et al. (2011). Angiopoietin 2 stimulates TIE2-expressing monocytes to suppress T cell activation and to promote regulatory T cell expansion. J. Immunol. 186, 4183-4190. doi: 10.4049/jimmunol.1002802.
9. Coffelt, S. B., Hughes, R., and Lewis, C. E. (2009). Tumor-associated macrophages: effectors of angiogenesis and tumor progression. Biochim. Biophys. Acta 1796, 11-18. doi: 10.1016/j.bbcan.2009.02.004.
10. Coffelt, S. B., Tal, A. O., Scholz, A., De Palma, M., Patel, S., Urbich, C., et al. (2010). Angiopoietin-2 regulates gene expression in TIE2-expressing monocytes and augments their inherent proangiogenic functions. Cancer Res. 70, 5270-5280. doi: 10.1158/0008-5472.CAN-10-0012.
11. Cramer, T., Yamanishi, Y., Clausen, B. E., Forster, I., Pawlinski, R., Mackman, N., et al. (2003). HIF-1alpha is essential for myeloid cell-mediated inflammation. Cell 112, 645-657. doi: 10.1016/S0092-8674(03)00154-5.
12. David Dong, Z. M., Aplin, A. C., and Nicosia, R. F. (2009). Regulation of angiogenesis by macrophages, dendritic cells, and circulating myelomonocytic cells. Curr. Pharm. Des. 15, 365-379. doi: 10.2174/138161209787315783.
13. de Souza, L. F., Jardim, F. R., Sauter, I. P., de Souza, M, and Bernard, E. A. (2008). High glucose increases RAW 264.7 macrophages activation by lipoteichoic acid from Staphylococcus aureus. Clin. Chim. Acta 398, 130-133. doi: 10.1016/j.cca.2008.09.007.
14. Desvergne, B., Michalik, L., and Wahli, W. (2006). Transcriptional regulation of metabolism. Physiol. Rev. 86, 465-514. doi: 10.1152/physrev.00025.2005.
15. Dirkx, A. E., Oude Egbrink, M. G., Wagstaff, J., and Griffioen, A. W. (2006). Monocyte/macrophage infiltration in tumors: modulators of angiogenesis. J. Leukoc. Biol. 80, 1183-1196. doi: 10.1189/jlb.0905495.
16. Ehses, J. A., Perren, A., Eppler, E., Ribaux, P., Pospisilik, J. A., Maor-Cahn, R., et al. (2007). Increased number of islet-associated macrophages in type 2 diabetes. Diabetes 56, 2356-2370. doi: 10.2337/db06-1650.
17. Eisele, N. A., Ruby, T., Jacobson, A., Manzanillo, P. S., Cox, J. S., Lam, L., et al. (2013). Salmonella require the fatty acid regulator PPARdelta for the establishment of a metabolic environment essential for long-term persistence. Cell Host Microbe 14, 171-182. doi: 10.1016/j.chom.2013.07.010.
18. Facciabene, A., Motz, G. T., and Coukos, G. (2012). T-regulatory cells: key players in tumor immune escape and angiogenesis. Cancer Res. 72, 2162-2171. doi: 10.1158/0008-5472.CAN-11-3687.
19. Fang, H. Y., Hughes, R., Murdoch, C., Coffelt, S. B., Biswas, S. K., Harris, A. L., et al. (2009). Hypoxia-inducible factors 1 and 2 are important transcriptional effectors in primary macrophages experiencing hypoxia. Blood 114, 844-859. doi: 10.1182/blood-2008-12-195941.
20. Fantin, A., Vieira, J. M., Gestri, G., Denti, L., Schwarz, Q., Prykhozhij, S., et al. (2010). Tissue macrophages act as cellular chaperones for vascular anastomosis downstream of VEGF-mediated endothelial tip cell induction. Blood 116, 829-840. doi: 10.1182/blood-2009-12-257832.
21. Ferraris, J. D., Persaud, P., Williams, C. K., Chen, Y., and Burg, M. B. (2002). cAMP-independent role of PKA in tonicity-induced transactivation of tonicity-responsive enhancer/osmotic response element-binding protein. Proc. Natl. Acad. Sci. U.S.A. 99, 16800-16805. doi: 10.1073/pnas.222659799.
22. Folkman, J. (2006). Angiogenesis. Annu. Rev. Med. 57:1-18. doi: 10.1146/annurev.med.57.121304.131306.
23. Geissmann, F., Manz, M. G., Jung, S., Sieweke, M. H., Merad, M., and Ley, K. (2010). Development of monocytes, macrophages, and dendritic cells. Science 327, 656-661. doi: 10.1126/science.1178331.
24. Gordon, S. (2003). Alternative activation of macrophages. Nat. Rev. Immunol. 3, 23-35. doi: 10.1038/nri978.
25. Halterman, J. A., Kwon, H. M., and Wamhoff, B. R. (2012). Tonicity-independent regulation of the osmosensitive transcription factor TonEBP (NFAT5). Am. J. Physiol. Cell Physiol. 302, C1-C8. doi: 10.1152/ajpcell.00327.2011.
26. Hamm, A., Veschini, L., Takeda, Y., Costa, S., Delamarre, E., Squadrito, M. L., et al. (2013). PHD2 regulates arteriogenic macrophages through TIE2 signalling. EMBO Mol. Med. 5, 843-857. doi: 10.1002/emmm.201302695.
27. Han, J., Lee, J. D., Bibbs, L., and Ulevitch, R. J. (1994). A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells. Science 265, 808-811.
28. Han, M. S., Jung, D. Y., Morel, C., Lakhani, S. A., Kim, J. K., Flavell, R. A., et al. (2013). JNK expression by macrophages promotes obesity-induced insulin resistance and inflammation. Science 339, 218-222. doi: 10.1126/science.1227568.
29. Haschemi, A., Kosma, P., Gille, L., Evans, C. R., Burant, C. F., Starkl, P., et al. (2012). The sedoheptulose kinase CARKL directs macrophage polarization through control of glucose metabolism. Cell Metab. 15, 813-826. doi: 10.1016/j.cmet.2012.04.023.
30. He, H, Xu, J. Y., Warren, C. M., Duan, D., Li, X. M., Wu, L., et al. (2012). Endothelial cells provide an instructive niche for the differentiation and functional polarization of M2-like macrophages. Blood 120, 3152-3162. doi: 10.1182/blood-2012-04-422758.
31. Huang, J. T., Welch, J. S., Ricote, M., Binder, C. J., Willson, T. M., Kelly, C., et al. (1999). Interleukin-4-dependent production of PPAR-gamma ligands in macrophages by 12/15-lipoxygenase. Nature 400, 378-382. doi: 10.1038/22572.
32. Irarrazabal, C. E., Liu, J. C., Burg, M. B., and Ferraris, J. D. (2004). ATM, a DNA damage-inducible kinase, contributes to activation by high NaCl of the transcription factor TonEBP/OREBP. Proc. Natl. Acad. Sci. U.S.A. 101, 8809-8814. doi: 10.1073/pnas.0403062101.
33. Jetten, N., Verbruggen, S., Gijbels, M. J., Post, M. J., De Winther, M. P., and Donners, M. (2014). Anti-inflammatory M2, but not pro-inflammatory M1 macrophages promote angiogenesis in vivo. Angiogenesis 17, 109-118. doi: 10.1007/s10456-013-9381-6.
34. Kanda, H., Tateya, S., Tamori, Y., Kotani, K., Hiasa, K., Kitazawa, R., et al. (2006). MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J. Clin. Invest. 116, 1494-1505. doi: 10.1172/JCI26498.
35. Kanter, J. E., Kramer, F., Barnhart, S., Averill, M, Vivekanandan-Giri, A., Vickery, T., et al. (2012). Diabetes promotes an inflammatory macrophage phenotype and atherosclerosis through acyl-CoA synthetase 1. Proc. Natl. Acad. Sci. U.S.A. 109, E715-E724. doi: 10.1073/pnas.1111600109.
36. Khan, B., Rangasamy, S., McGuire, P. G., and Howdieshell, T. R. (2013). The role of monocyte subsets in myocutaneous revascularization. J. Surg. Res. 183, 963-975. doi: 10.1016/j.jss.2013.02.019.
37. Kleinewietfeld, M., Manzel, A., Titze, J., Kvakan, H., Yosef, N., Linker, R. A., et al. (2013). Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells. Nature 496, 518-522. doi: 10.1038/nature11868.
38. Ko, B. C., Lam, A. K., Kapus, A., Fan, L., Chung, S. K., and Chung, S. (2002). Fyn and p38 signaling are both required for maximal hypertonic activation of the osmotic response element-binding protein/tonicity-responsive enhancer-binding protein (OREBP/TonEBP). J. Biol. Chem. 277, 46085-46092. doi: 10.1074/jbc.M208138200.
39. Kopp, C., Linz, P., Dahlmann, A., Hammon, M., Jantsch, J., Muller, D. N., et al. (2013). 23Na magnetic resonance imaging-determined tissue sodium in healthy subjects and hypertensive patients. Hypertension 61, 635-640. doi: 10.1161/HYPERTENSIONAHA.111.00566.
40. Kopp, C., Linz, P., Hammon, M., Schofl, C., Grauer, M., Eckardt, K. U., et al. (2012b). Seeing the sodium in a patient with hypernatremia. Kidney Int. 82, 1343-1344. doi: 10.1038/ki.2012.314.
41. Kopp, C., Linz, P., Wachsmuth, L., Dahlmann, A., Horbach, T., Schofl, C., et al. (2012a). (23)Na magnetic resonance imaging of tissue sodium. Hypertension 59, 167-172. doi: 10.1161/HYPERTENSIONAHA.111.183517.
42. Krausz, S., Garcia, S., Ambarus, C. A., de Launay, D., Foster, M., Naiman, B., et al. (2012). Angiopoietin-2 promotes inflammatory activation of human macrophages and is essential for murine experimental arthritis. Ann. Rheum. Dis. 71, 1402-1410. doi: 10.1136/annrheumdis-2011-200718.
43. Kuper, C., Steinert, D., Fraek, M. L., Beck, F. X., and Neuhofer, W. (2009). EGF receptor signaling is involved in expression of osmoprotective TonEBP target gene aldose reductase under hypertonic conditions. Am. J. Physiol. Renal Physiol. 296, F1100-F1108. doi: 10.1152/ajprenal.90402.2008.
44. Lang, F., Bohmer, C., Palmada, M., Seebohm, G., Strutz-Seebohm, N., and Vallon, V. (2006). (Patho)physiological significance of the serum-and glucocorticoid-inducible kinase isoforms. Physiol. Rev. 86, 1151-1178. doi: 10.1152/physrev.00050.2005.
45. Lewis, C. E., De Palma, M., and Naldini, L. (2007). Tie2-expressing monocytes and tumor angiogenesis: regulation by hypoxia and angiopoietin-2. Cancer Res. 67, 8429-8432. doi: 10.1158/0008-5472.CAN-07-1684.
46. Locati, M., Mantovani, A., and Sica, A. (2013). Macrophage activation and polarization as an adaptive component of innate immunity. Adv. Immunol. 120, 163-184. doi: 10.1016/B978-0-12-417028-5.00006-5.
47. Low-Marchelli, J. M., Ardi, V. C., Vizcarra, E. A., van Rooijen, N., Quigley, J. P., and Yang, J. (2013). Twist1 induces CCL2 and recruits macrophages to promote angiogenesis. Cancer Res. 73, 662-671. doi: 10.1158/0008-5472.CAN-12-0653.
48. Lumeng, C. N., Bodzin, J. L., and Saltiel, A. R. (2007a). Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J. Clin. Invest. 117, 175-184. doi: 10.1172/JCI29881.
49. Lumeng, C. N., Deyoung, S. M., and Saltiel, A. R. (2007b). Macrophages block insulin action in adipocytes by altering expression of signaling and glucose transport proteins. Am. J. Physiol. Endocrinol. Metab. 292:E166-E174. doi: 10.1152/ajpendo.00284.2006.
50. Lutz, M. B., and Kurts, C. (2009). Induction of peripheral CD4+ T-cell tolerance and CD8+ T-cell cross-tolerance by dendritic cells. Eur. J. Immunol. 39, 2325-2330. doi: 10.1002/eji.200939548.
51. Machnik, A., Dahlmann, A., Kopp, C., Goss, J., Wagner, H., van Rooijen, N., et al. (2010). Mononuclear phagocyte system depletion blocks interstitial tonicity-responsive enhancer binding protein/vascular endothelial growth factor C expression and induces salt-sensitive hypertension in rats. Hypertension 55, 755-761. doi: 10.1161/HYPERTENSIONAHA.109.143339.
52. Machnik, A., Neuhofer, W., Jantsch, J., Dahlmann, A., Tammela, T., Machura, K., et al. (2009). Macrophages regulate salt-dependent volume and blood pressure by a vascular endothelial growth factor-C-dependent buffering mechanism. Nat. Med. 15, 545-552. doi: 10.1038/nm.1960.
53. Mantovani, A., Biswas, S. K., Galdiero, M. R., Sica, A., and Locati, M. (2013). Macrophage plasticity and polarization in tissue repair and remodelling. J. Pathol. 229, 176-185. doi: 10.1002/path.4133.
54. Marchetti, V., Yanes, O., Aguilar, E., Wang, M., Friedlander, D., Moreno, S., et al. (2011). Differential macrophage polarization promotes tissue remodeling and repair in a model of ischemic retinopathy. Sci. Rep. 1:76. doi: 10.1038/srep00076.
55. Martel, C., Li, W., Fulp, B., Platt, A. M., Gautier, E. L., Westerterp, M., et al. (2013). Lymphatic vasculature mediates macrophage reverse cholesterol transport in mice. J. Clin. Invest. 123, 1571-1579. doi: 10.1172/JCI63685.
56. Mazzieri, R., Pucci, F., Moi, D., Zonari, E., Ranghetti, A., Berti, A., et al. (2011). Targeting the ANG2/TIE2 axis inhibits tumor growth and metastasis by impairing angiogenesis and disabling rebounds of proangiogenic myeloid cells. Cancer Cell 19, 512-526. doi: 10.1016/j.ccr.2011.02.005.
57. Medzhitov, R. (2008). Origin and physiological roles of inflammation. Nature 454, 428-435. doi: 10.1038/nature07201.
58. Morancho, B., Minguillon, J., Molkentin, J. D., Lopez-Rodriguez, C., and Aramburu, J. (2008). Analysis of the transcriptional activity of endogenous NFAT5 in primary cells using transgenic NFAT-luciferase reporter mice. BMC Mol. Biol. 9:13. doi: 10.1186/1471-2199-9-13.
59. Mosser, D. M., and Edwards, J. P. (2008). Exploring the full spectrum of macrophage activation. Nat. Rev. Immunol. 8, 958-969. doi: 10.1038/nri2448.
60. Muller, S., Quast, T., Schroder, A., Hucke, S., Klotz, L., Jantsch, J., et al. (2013). Salt-dependent chemotaxis of macrophages. PLoS ONE 8:e73439. doi: 10.1371/journal.pone.0073439.
61. Murdoch, C., Muthana, M., Coffelt, S. B., and Lewis, C. E. (2008). The role of myeloid cells in the promotion of tumour angiogenesis. Nat. Rev. Cancer 8, 618-631. doi: 10.1038/nrc2444.
62. Murray, P. J., and Wynn, T. A. (2011). Protective and pathogenic functions of macrophage subsets. Nat. Rev. Immunol. 11, 723-737. doi: 10.1038/nri3073.
63. Nadkarni, V., Gabbay, K. H., Bohren, K. M., and Sheikh-Hamad, D. (1999). Osmotic response element enhancer activity. Regulation through p38 kinase and mitogen-activated extracellular signal-regulated kinase kinase. J. Biol. Chem. 274, 20185-20190.
64. Nagy, L., Szanto, A., Szatmari, I., and Szeles, L. (2012). Nuclear hormone receptors enable macrophages and dendritic cells to sense their lipid environment and shape their immune response. Physiol. Rev. 92, 739-789. doi: 10.1152/physrev.00004.2011.
65. Naldini, A., Pucci, A., Bernini, C., and Carraro, F. (2003). Regulation of angiogenesis by Th1-and Th2-type cytokines. Curr. Pharm. Des. 9, 511-519. doi: 10.2174/1381612033391423.
66. Nucera, S., Biziato, D., and De Palma, M. (2011). The interplay between macrophages and angiogenesis in development, tissue injury and regeneration. Int. J. Dev. Biol. 55, 495-503. doi: 10.1387/ijdb.103227sn.
67. Odegaard, J. I., Ricardo-Gonzalez, R, Goforth, M. H., Morel, C. R., Subramanian, V., Mukundan, L., et al. (2007). Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance. Nature 447, 1116-1120. doi: 10.1038/nature05894.
68. Odegaard, JI., and Chawla, A. (2013). The immune system as a sensor of the metabolic state. Immunity 38, 644-654. doi: 10.1016/j.immuni.2013.04.001.
69. Owen, J. L., and Mohamadzadeh, M. (2013). Macrophages and chemokines as mediators of angiogenesis. Front. Physiol. 4:159. doi: 10.3389/fphys.2013.00159.
70. Pal, D., Dasgupta, S., Kundu, R., Maitra, S., Das, G., Mukhopadhyay, S., et al. (2012). Fetuin-A acts as an endogenous ligand of TLR4 to promote lipid-induced insulin resistance. Nat. Med. 18, 1279-1285. doi: 10.1038/nm.2851.
71. Pollard, J. W. (2004). Tumour-educated macrophages promote tumour progression and metastasis. Nat. Rev. Cancer 4, 71-78. doi: 10.1038/nrc1256.
72. Pollard, J. W. (2009). Trophic macrophages in development and disease. Nat. Rev. Immunol. 9, 259-270. doi: 10.1038/nri2528.
73. Potente, M., Gerhardt, H., and Carmeliet, P. (2011). Basic and therapeutic aspects of angiogenesis. Cell 146, 873-887. doi: 10.1016/j.cell.2011.08.039.
74. Ricote, M., Huang, J., Fajas, L., Li, A., Welch, J., Najib, J., et al. (1998). Expression of the peroxisome proliferator-activated receptor gamma (PPARgamma) in human atherosclerosis and regulation in macrophages by colony stimulating factors and oxidized low density lipoprotein. Proc. Natl. Acad. Sci. U.S.A. 95, 7614-7619.
75. Roth, I., Leroy, V., Kwon, H. M., Martin, P. Y., Feraille, E., and Hasler, U. (2010). Osmoprotective transcription factor NFAT5/TonEBP modulates nuclear factor-kappaB activity. Mol. Biol. Cell 21, 3459-3474. doi: 10.1091/mbc.E10-02-0133.
76. Saharinen, P., and Alitalo, K. (2011). The yin, the yang, and the angiopoietin-1. J. Clin. Invest. 121, 2157-2159. doi: 10.1172/JCI58196.
77. Saharinen, P., Bry, M., and Alitalo, K. (2010). How do angiopoietins Tie in with vascular endothelial growth factors? Curr. Opin. Hematol. 17, 198-205. doi: 10.1097/MOH.0b013e3283386673.
78. Schulze-Osthoff, K., Risau, W., Vollmer, E., and Sorg, C. (1990). In situ detection of basic fibroblast growth factor by highly specific antibodies. Am. J. Pathol. 137, 85-92.
79. Shapiro, L., and Dinarello, C. A. (1995). Osmotic regulation of cytokine synthesis in vitro. Proc. Natl. Acad. Sci. U.S.A. 92, 12230-12234.
80. Shi, H., Kokoeva, M. V., Inouye, K., Tzameli, I., Yin, H., and Flier, J. S. (2006). TLR4 links innate immunity and fatty acid-induced insulin resistance. J. Clin. Invest. 116, 3015-3025. doi: 10.1172/JCI28898.
81. Sjostrom, M., Stenstrom, K., Eneling, K., Zwiller, J., Katz, A. I., Takemori, H., et al. (2007). SIK1 is part of a cell sodium-sensing network that regulates active sodium transport through a calcium-dependent process. Proc. Natl. Acad. Sci. U.S.A. 104, 16922-16927. doi: 10.1073/pnas.0706838104.
82. Solinas, G., Vilcu, C., Neels, J. G., Bandyopadhyay, G. K., Luo, J. L., Naugler, W., et al. (2007). JNK1 in hematopoietically derived cells contributes to diet-induced inflammation and insulin resistance without affecting obesity. Cell Metab. 6, 386-397. doi: 10.1016/j.cmet.2007.09.011.
83. Stabile, E., Burnett, M. S., Watkins, C., Kinnaird, T., Bachis, A., la Sala, A., et al. (2003). Impaired arteriogenic response to acute hindlimb ischemia in CD4-knockout mice. Circulation 108, 205-210. doi: 10.1161/01.CIR.0000079225.50817.71.
84. Stabile, E., Kinnaird, T., la Sala, A., Hanson, S. K., Watkins, C., Campia, U., et al. (2006). CD8+ T lymphocytes regulate the arteriogenic response to ischemia by infiltrating the site of collateral vessel development and recruiting CD4+ mononuclear cells through the expression of interleukin-16. Circulation 113, 118-124. doi: 10.1161/CIRCULATIONAHA.105.576702.
85. Starnes, T., Robertson, M., Sledge, G., Kelich, S., Nakshatri, H., Broxmeyer, H. E., et al. (2001). IL-17F, a novel cytokine selectively expressed in activated T-cells and monocytes, regulates angiogenesis and endothelial cell cytokine production. Blood 98, 818a-819a.
86. Swirski, F. K., Nahrendorf, M., Etzrodt, M., Wildgruber, M., Cortez-Retamozo, V., Panizzi, P, et al. (2009). Identification of splenic reservoir monocytes and their deployment to inflammatory sites. Science 325, 612-616. doi: 10.1126/science.1175202.
87. Szanto, A., Balint, B. L., Nagy, Z. S., Barta, E., Dezso, B., Pap, A., et al. (2010). STAT6 transcription factor is a facilitator of the nuclear receptor PPARgamma-regulated gene expression in macrophages and dendritic cells. Immunity 33, 699-712. doi: 10.1016/j.immuni.2010.11.009.
88. Takeda, Y., Costa, S., Delamarre, E., Roncal, C., Leite de Oliveira, R., Squadrito, M. L., et al. (2011). Macrophage skewing by Phd2 haplodeficiency prevents ischaemia by inducing arteriogenesis. Nature 479, 122-126. doi: 10.1038/nature10507.
89. Tauber, A. I. (2003). Metchnikoff and the phagocytosis theory. Nat. Rev. Mol. Cell Biol. 4, 897-901. doi: 10.1038/nrm1244.
90. Titze, J. (2014). Sodium balance is not just a renal affair. Curr. Opin. Nephrol. Hypertens. 23, 101-105. doi: 10.1097/01.mnh.0000441151.55320.c3.
91. Titze, J., and Machnik, A. (2010). Sodium sensing in the interstitium and relationship to hypertension. Curr. Opin. Nephrol. Hypertens. 19, 385-392. doi: 10.1097/MNH.0b013e32833aeb3b.
92. Vats, D., Mukundan, L., Odegaard, J. I., Zhang, L., Smith, K. L., Morel, C. R., et al. (2006). Oxidative metabolism and PGC-1beta attenuate macrophage-mediated inflammation. Cell Metab. 4, 13-24. doi: 10.1016/j.cmet.2006.05.011.
93. Weisberg, S. P., Hunter, D., Huber, R., Lemieux, J., Slaymaker, S., Vaddi, K., et al. (2006). CCR2 modulates inflammatory and metabolic effects of high-fat feeding. J. Clin. Invest. 116, 115-124. doi: 10.1172/JCI24335.
94. Weisberg, S. P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R. L., and Ferrante, A. W. Jr. (2003). Obesity is associated with macrophage accumulation in adipose tissue. J. Clin. Invest. 112, 1796-808. doi: 10.1172/JCI19246.
95. Wiig, H., Schroder, A., Neuhofer, W., Jantsch, J., Kopp, C., Karlsen, T. V., et al. (2013). Immune cells control skin lymphatic electrolyte homeostasis and blood pressure. J. Clin. Invest. 123, 2803-2815. doi: 10.1172/JCI60113.
96. Wu, C., Yosef, N., Thalhamer, T., Zhu, C., Xiao, S., Kishi, Y., et al. (2013). Induction of pathogenic TH17 cells by inducible salt-sensing kinase SGK1. Nature 496, 513-517. doi: 10.1038/nature11984.
97. Xiong, M., Elson, G., Legarda, D., and Leibovich, S. J. (1998). Production of vascular endothelial growth factor by murine macrophages: regulation by hypoxia, lactate, and the inducible nitric oxide synthase pathway. Am. J. Pathol. 153, 587-598. doi: 10.1016/S0002-9440(10)65601-5.
98. Xu, H., Barnes, G. T., Yang, Q., Tan, G., Yang, D., Chou, C. J., et al. (2003). Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J. Clin. Invest. 112, 1821-1830. doi: 10.1172/JCI19451.
99. Yang, S., Kim, J., Ryu, J. H., Oh, H., Chun, C. H., Kim, B. J., et al. (2010). Hypoxia-inducible factor-2 alpha is a catabolic regulator of osteoarthritic cartilage destruction. Nat. Med. 16, 687-693. doi: 10.1038/Nm.2153.
100. Zajac, E., Schweighofer, B., Kupriyanova, T. A., Juncker-Jensen, A., Minder, P., Quigley, J. P., et al. (2013). Angiogenic capacity of M1-and M2-polarized macrophages is determined by the levels of TIMP-1 complexed with their secreted proMMP-9. Blood 122, 4054-4067. doi: 10.1182/blood-2013-05-501494.
101. Zhou, X., Ferraris, J. D., Dmitrieva, N. I., Liu, Y., and Burg, M. B. (2008). MKP-1 inhibits high NaCl-induced activation of p38 but does not inhibit the activation of TonEBP/OREBP: opposite roles of p38alpha and p38delta. Proc. Natl. Acad. Sci. U.S.A. 105, 5620-5625. doi: 10.1073/pnas.0801453105.
102. Zhou, X., Izumi, Y., Burg, M. B., and Ferraris, J. D. (2011). Rac1/osmosensing scaffold for MEKK3 contributes via phospholipase C-gamma1 to activation of the osmoprotective transcription factor NFAT5. Proc. Natl. Acad. Sci. U.S.A. 108, 12155-12160. doi: 10.1073/pnas.1108107108.