Osteopontin in macrophage function

Susan R. Rittling

doi:10.1017/S1462399411001839

Osteopontin in macrophage function

Published online by Cambridge University Press: 26 April 2011

Susan R. Rittling

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Susan R. Rittling: Affiliation:
The Forsyth Institute, 245 First St, Cambridge, MA 02142, USA. E-mail: srittling@forsyth.org

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Abstract

The secreted phosphorylated protein osteopontin (OPN) is expressed in a variety of tissues and bodily fluids, and is associated with pathologies including tissue injury, infection, autoimmune disease and cancer. Macrophages are ubiquitous, heterogeneous cells that mediate aspects of cell and tissue damage in all these pathologies. Here, the role of OPN in macrophage function is reviewed. OPN is expressed in macrophage cells in multiple pathologies, and the regulation of its expression in these cells has been described in vitro. The protein has been implicated in multiple functions of macrophages, including cytokine expression, expression of inducible nitric oxide synthase, phagocytosis and migration. Indeed, the role of OPN in cells of the macrophage lineage might underlie its physiological role in many pathologies. However, there are numerous instances where the published literature is inconsistent, especially in terms of OPN function in vitro. Although the heterogeneity of OPN and its receptors, or of macrophages themselves, might underlie some of these inconsistencies, it is important to understand the role of OPN in macrophage biology in order to exploit its function therapeutically.

Type: Review Article
Information: Expert Reviews in Molecular Medicine , Volume 13 , March 2011 , e15

DOI: https://doi.org/10.1017/S1462399411001839 [Opens in a new window]
Copyright: Copyright © Cambridge University Press 2011

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References

1Senger, D.R. et al. (1989) Purification of a human milk protein closely similar to tumor-secreted phosphoproteins and osteopontin. Biochimica Biophysica Acta 966, 43-48CrossRef Google Scholar

2Oldberg, A., Franzen, A. and Heinegard, D. (1986) Cloning and sequence analysis of rat bone sialoprotein (osteopontin) cDNA reveals an Arg-Gly-Asp cell-binding sequence. Proceedings of the National Academy of Sciences of the United States of America 83, 8819-8823Google Scholar

3Brown, L.F. et al. (1992) Expression and distribution of osteopontin in human tissues: widespread association with luminal epithelial surfaces. Molecular Biology of the Cell 3, 1169-1180Google Scholar

4Rittling, S.R. et al. (2003) Osteopontin, a surprisingly flexible cytokine: functions revealed from knockout mice. In Contemporary Immunology: Cytokine Knockouts (2nd edn) (Fantuzzi, G., ed.), pp. 379-393, Humana Press Inc., Totowa, NJCrossRef Google Scholar

5Weber, G.F. and Cantor, H. (1996) The immunology of Eta-1/osteopontin. Cytokine and Growth Factor Reviews 7, 241-248CrossRef Google Scholar PubMed

6Rittling, S.R. and Chambers, A.F. (2004) Role of osteopontin in tumour progression. British Journal of Cancer 90, 1877-1881CrossRef Google Scholar PubMed

7Ramaiah, S.K. and Rittling, S. (2007) Role of osteopontin in regulating hepatic inflammatory responses and toxic liver injury. Expert Opinion on Drug Metabolism and Toxicology 3, 519-526CrossRef Google Scholar PubMed

8Giachelli, C. (2005) Inducers and inhibitors of biomineralization: lessons from pathological calcification. Orthodontics and Craniofacial Research 8, 229-231CrossRef Google Scholar PubMed

9Scatena, M., Liaw, L. and Giachelli, C.M. (2007) Osteopontin: a multifunctional molecule regulating chronic inflammation and vascular disease. Arteriosclerosis, Thrombosis, and Vascular Biology 27, 2302-2309Google Scholar

10Christensen, B. et al. (2007) Cell type-specific post-translational modifications of mouse osteopontin are associated with different adhesive properties. Journal of Biological Chemistry 282, 19463-19472CrossRef Google Scholar PubMed

11Cao, Z. et al. (2008) A novel functional motif of osteopontin for human lymphocyte migration and survival. Molecular Immunology 45, 3683-3692Google Scholar

12Zheng, W. et al. (2009) Role of osteopontin in induction of monocyte chemoattractant protein 1 and macrophage inflammatory protein 1beta through the NF-kappaB and MAPK pathways in rheumatoid arthritis. Arthritis and Rheumatism 60, 1957-1965CrossRef Google Scholar PubMed

13Hu, D.D. et al. (1995) A biochemical characterization of the binding of osteopontin to integrins αvβ1 and αvβ5. Journal of Biological Chemistry 270, 26232-26238Google Scholar

14Hu, D.D., Hoyer, J.R. and Smith, J.W. (1995) Calcium suppresses cell adhesion to osteopontin by attenuating binding affinity for integrin αvβ3. Journal of Biological Chemistry 270, 9917-9925CrossRef Google Scholar

15Bayless, K.J. et al. (1998) Osteopontin is a ligand for the α4β1 integrin. Journal of Cell Science 111, 1165-1174CrossRef Google Scholar PubMed

16Barry, S.T. et al. (2000) Analysis of the alpha4beta1 integrin–osteopontin interaction. Experimental Cell Research 258, 342-351Google Scholar

17Yokosaki, Y. et al. (1999) The integrin alpha(9)beta(1) binds to a novel recognition sequence (SVVYGLR) in the thrombin-cleaved amino-terminal fragment of osteopontin. Journal of Biological Chemistry 274, 36328-36334CrossRef Google Scholar

18Barry, S.T. et al. (2000) A regulated interaction between alpha5beta1 integrin and osteopontin. Biochemical and Biophysical Research Communications 267, 764-769CrossRef Google Scholar PubMed

19Yokosaki, Y. et al. (2005) Distinct structural requirements for binding of the integrins alphavbeta6, alphavbeta3, alphavbeta5, alpha5beta1 and alpha9beta1 to osteopontin. Matrix Biology 24, 418-427Google Scholar

20Denda, S., Reichardt, L.F. and Müller, U. (1998) Identification of osteopontin as a novel ligand for the integrin α8β1 and potential roles for this integrin–ligand interaction in kidney morphogenesis. Molecular Biology of the Cell 9, 1425-1435CrossRef Google Scholar PubMed

21Schack, L. et al. (2009) Osteopontin enhances phagocytosis through a novel osteopontin receptor, the {alpha}X{beta}2 integrin. Journal of Immunology 182, 6943-6950CrossRef Google Scholar

22Weber, G.F. et al. (1996) Receptor-ligand interaction between CD44 and osteopontin (ETA-1). Science 271, 509-512CrossRef Google Scholar

23Smith, L.L. et al. (1999) CD44 is not an adhesive receptor for osteopontin. Journal of Cellular Biochemistry 73, 20-303.0.CO;2-3>CrossRef Google Scholar

24Katagiri, Y.U. et al. (1999) CD44 variants but not CD44s cooperate with beta1-containing integrins to permit cells to bind to osteopontin independently of arginine–glycine–aspartic acid, thereby stimulating cell motility and chemotaxis. Cancer Research 59, 219-226Google Scholar

25Weber, G.F. et al. (2002) Phosphorylation-dependent interaction of osteopontin with its receptors regulates macrophage migration and activation. Journal of Leukocyte Biology 72, 752-761Google Scholar

26Jain, A. et al. (2002) Three SIBLINGs (SmallIntegrin-Binding LIgand, N-linked Glycoproteins) enhance factor H's cofactor activity enabling MCP-like cellular evasion of complement-mediated attack. Journal of Biological Chemistry 277, 13700-13708Google Scholar

27Rittling, S.R. et al. (2002) Tumor-derived osteopontin is soluble, not matrix associated. Journal of Biological Chemistry 277, 9175-9182CrossRef Google Scholar

28Christensen, B. et al. (2010) Osteopontin is cleaved at multiple sites close to its integrin-binding motifs in milk and is a novel substrate for plasmin and cathepsin D. Journal of Biological Chemistry 285, 7929-7937Google Scholar

29Agnihotri, R. et al. (2001) Osteopontin, a novel substrate for matrix metalloproteinase-3 (stromelysin-1) and matrix metalloproteinase-7 (matrilysin). Journal of Biological Chemistry 276, 28261-28267Google Scholar

30Sharif, S.A. et al. (2009) Thrombin-activatable carboxypeptidase B cleavage of osteopontin regulates neutrophil survival and synoviocyte binding in rheumatoid arthritis. Arthritis and Rheumatism 60, 2902-2912Google Scholar

31Zohar, R. et al. (2000) Intracellular osteopontin is an integral component of the CD44-ERM complex involved in cell migration. Journal of Cellular Physiology 184, 118-1303.0.CO;2-Y>CrossRef Google Scholar PubMed

32Zhu, B. et al. (2004) Osteopontin modulates CD44-dependent chemotaxis of peritoneal macrophages through G-protein-coupled receptors: evidence of a role for an intracellular form of osteopontin. Journal of Cellular Physiology 198, 155-167Google Scholar

33Cantor, H. and Shinohara, M.L. (2009) Regulation of T-helper-cell lineage development by osteopontin: the inside story. Nature Reviews. Immunology 9, 137-141CrossRef Google Scholar PubMed

34Inoue, M. et al. (2010) Cutting edge: critical role of intracellular osteopontin in antifungal innate immune responses. Journal of Immunology 186, 19-23Google Scholar

35Rittling, S.R. et al. (1998) Mice lacking osteopontin show normal development and bone structure but display altered osteoclast formation in vitro. Journal of Bone amd Mineral Research 13, 1101-1111CrossRef Google Scholar PubMed

36Liaw, L. et al. (1998) Altered wound healing in mice lacking a functional osteopontin gene (spp1). Journal of Clinical Investigation 101, 1468-1478CrossRef Google Scholar PubMed

37Lund, S., Giachelli, C. and Scatena, M. (2009) The role of osteopontin in inflammatory processes. Journal of Cell Communication and Signaling 3, 311-322CrossRef Google Scholar PubMed

38Wang, K.X. and Denhardt, D.T. (2008) Osteopontin: role in immune regulation and stress responses. Cytokine and Growth Factor Reviews 19, 333-345Google Scholar

39Buback, F. et al. (2009) Osteopontin and the skin: multiple emerging roles in cutaneous biology and pathology. Experimental Dermatology 18, 750-759CrossRef Google Scholar

40Bellahcene, A. et al. (2008) Small integrin-binding ligand N-linked glycoproteins (SIBLINGs): multifunctional proteins in cancer. Nature Reviews. Cancer 8, 212-226CrossRef Google Scholar PubMed

41Atkins, K. et al. (1998) Coordinate expression of OPN and associated receptors during monocyte/macrophage differentiation of HL-60 cells. Journal of Cellular Physiology 175, 229-2373.0.CO;2-3>CrossRef Google Scholar PubMed

42Oyama, Y. et al. (2002) PPARgamma ligand inhibits osteopontin gene expression through interference with binding of nuclear factors to A/T-rich sequence in THP-1 cells. Circulation Research 90, 348-355Google Scholar

43Suzuki, H. et al. (2009) The transcriptional network that controls growth arrest and differentiation in a human myeloid leukemia cell line. Nature Genetics 41, 553-562Google Scholar

44Atkins, K.B., Simpson, R.U. and Somerman, M.J. (1997) Stimulation of osteopontin mRNA expression in HL-60 cells is independent of differentiation. Archives of Biochemistry and Biophysics 343, 157-163CrossRef Google Scholar PubMed

45Nakamachi, T. et al. (2007) PPARalpha agonists suppress osteopontin expression in macrophages and decrease plasma levels in patients with type 2 diabetes. Diabetes 56, 1662-1670CrossRef Google Scholar PubMed

46Li, X., O'Regan, A.W. and Berman, J.S. (2003) IFN-gamma induction of osteopontin expression in human monocytoid cells. Journal of Interferon and Cytokine Research 23, 259-265CrossRef Google Scholar PubMed

47Miyazaki, Y. et al. (1995) Expression of osteopontin in a macrophage cell line and in transgenic mice with pulmonary fibrosis resulting from the lung expression of a tumor necrosis factor-alpha transgene. Annals of the New York Academy of Sciences 760, 334-341CrossRef Google Scholar

48Wuthrich, R.P. et al. (1998) Enhanced osteopontin expression and macrophage infiltration in MRL-Fas(lpr) mice with lupus nephritis. Autoimmunity 28, 139-150CrossRef Google Scholar PubMed

49Konno, S. et al. (2006) Interleukin-10 and Th2 cytokines differentially regulate osteopontin expression in human monocytes and dendritic cells. Journal of Interferon and Cytokine Research 26, 562-567CrossRef Google Scholar PubMed

50Samuvel, D.J. et al. (2010) Adipocyte-mononuclear cell interaction, Toll-like receptor 4 activation, and high glucose synergistically up-regulate osteopontin expression via an interleukin 6-mediated mechanism. Journal of Biological Chemistry 285, 3916-3927CrossRef Google Scholar PubMed

51Rollo, E.E. and Denhardt, D.T. (1996) Differential effects of osteopontin on the cytotoxic activity of macrophages from young and old mice. Immunology 88, 642-647CrossRef Google Scholar PubMed

52Solinas, G. et al. (2010) Tumor-conditioned macrophages secrete migration-stimulating factor: a new marker for m2-polarization, influencing tumor cell motility. Journal of Immunology 185, 642-652CrossRef Google Scholar PubMed

53Ogawa, D. et al. (2005) Liver X receptor agonists inhibit cytokine-induced osteopontin expression in macrophages through interference with activator protein-1 signaling pathways. Circulation Research 96, e59-e67Google Scholar

54Guo, H. et al. (2001) Osteopontin is a negative feedback regulator of nitric oxide synthesis in murine macrophages. Journal of Immunology 166, 1079-1086CrossRef Google Scholar PubMed

55Gao, C. et al. (2004) S-nitrosylation of heterogeneous nuclear ribonucleoprotein A/B regulates osteopontin transcription in endotoxin-stimulated murine macrophages. Journal of Biological Chemistry 279, 11236-11243Google Scholar

56Takahashi, F. et al. (2000) Osteopontin is induced by nitric oxide in RAW 264.7 cells. IUBMB Life 49, 217-221CrossRef Google Scholar PubMed

57Gao, C. et al. (2005) Transcriptional regulatory functions of heterogeneous nuclear ribonucleoprotein-U and -A/B in endotoxin-mediated macrophage expression of osteopontin. Journal of Immunology 175, 523-530CrossRef Google Scholar

58Zhao, W. et al. (2010) Differential expression of intracellular and secreted osteopontin isoforms by murine macrophages in response to toll-like receptor agonists. Journal of Biological Chemistry 285, 20452-20461Google Scholar

59Nares, S. et al. (2009) Rapid myeloid cell transcriptional and proteomic responses to periodontopathogenic porphyromonas gingivalis. American Journal of Pathology 174, 1400-1414CrossRef Google Scholar PubMed

60Koguchi, Y. et al. (2002) Penicillium marneffei causes osteopontin-mediated production of interleukin-12 by peripheral blood mononuclear cells. Infection and Immunity 70, 1042-1048Google Scholar

61Khajoee, V. et al. (2006) Novel roles of osteopontin and CXC chemokine ligand 7 in the defence against mycobacterial infection. Clinical and Experimental Immunology 143, 260-268Google Scholar

62Wang, Y. et al. (2000) Increased expression of osteopontin in activated Kupffer cells and hepatic macrophages during macrophage migration in Propionibacterium acnes-treated rat liver. Journal of Gastroenterology 35, 696-701Google Scholar

63Ragno, S. et al. (2001) Changes in gene expression in macrophages infected with Mycobacterium tuberculosis: a combined transcriptomic and proteomic approach. Immunology 104, 99-108CrossRef Google Scholar PubMed

64van der Windt, G.J. et al. (2009) Osteopontin is not crucial to protective immunity during murine tuberculosis. Immunology 128, e766-e776CrossRef Google Scholar

65Kohan, M. et al. (2007) Enhanced osteopontin expression in a murine model of allergen-induced airway remodelling. Clinical and Experimental Allergy 37, 1444-1454Google Scholar

66Prasse, A. et al. (2009) Essential role of osteopontin in smoking-related interstitial lung diseases. American Journal of Pathology 174, 1683-1691Google Scholar

67Nomiyama, T. et al. (2007) Osteopontin mediates obesity-induced adipose tissue macrophage infiltration and insulin resistance in mice. Journal of Clinical Investigation 117, 2877-2888CrossRef Google Scholar PubMed

68Kiefer, F.W. et al. (2008) Osteopontin expression in human and murine obesity: extensive local up-regulation in adipose tissue but minimal systemic alterations. Endocrinology 149, 1350-1357Google Scholar

69Brown, L.F. et al. (1994) Osteopontin expression and distribution in human carcinomas. American Journal of Pathology 145, 610-623Google Scholar

70Kim, J. et al. (2006) Elevated plasma osteopontin levels in patients with hepatocellular carcinoma. American Journal of Gastroenterology 101, 2051-2059CrossRef Google Scholar PubMed

71O'Brien, E.R. et al. (1994) Osteopontin is synthesized by macrophage, smooth muscle, and endothelial cells in primary and restenotic human coronary atherosclerotic plaques. Arteriosclerosis and Thrombosis 14, 1648-1656Google Scholar

72Speer, M.Y. et al. (2002) Inactivation of the osteopontin gene enhances vascular calcification of matrix Gla protein-deficient mice: evidence for osteopontin as an inducible inhibitor of vascular calcification in vivo. Journal of Experimental Medicine 196, 1047-1055CrossRef Google Scholar PubMed

73Hirota, S. et al. (1993) Expression of osteopontin messenger RNA by macrophages in atherosclerotic plaques. A possible association with calcification. American Journal of Pathology 143, 1003-1008Google Scholar PubMed

74Choi, J.S. et al. (2003) Induction and temporal changes of osteopontin mRNA and protein in the brain following systemic lipopolysaccharide injection. Journal of Neuroimmunology 141, 65-73CrossRef Google Scholar PubMed

75Iczkiewicz, J., Rose, S. and Jenner, P. (2005) Increased osteopontin expression following intranigral lipopolysaccharide injection in the rat. European Journal of Neuroscience 21, 1911-1920Google Scholar

76Yan, Y.P. et al. (2009) Osteopontin is a mediator of the lateral migration of neuroblasts from the subventricular zone after focal cerebral ischemia. Neurochemistry International 55, 826-832CrossRef Google Scholar PubMed

77Fu, Y. et al. (2004) Spinal root avulsion-induced upregulation of osteopontin expression in the adult rat spinal cord. Acta Neuropathologica (Berlin) 107, 8-16CrossRef Google Scholar PubMed

78Zhao, C. et al. (2008) Osteopontin is extensively expressed by macrophages following CNS demyelination but has a redundant role in remyelination. Neurobiology of Disease 31, 209-217CrossRef Google Scholar

79Harada, K. et al. (2003) Osteopontin is involved in the formation of epithelioid granuloma and bile duct injury in primary biliary cirrhosis. Pathology International 53, 8-17Google Scholar

80Murry, C.E. et al. (1994) Macrophages express osteopontin during repair of myocardial necrosis. American Journal of Pathology 145, 1450-1462Google Scholar PubMed

81Komatsubara, I. et al. (2003) Spatially and temporally different expression of osteonectin and osteopontin in the infarct zone of experimentally induced myocardial infarction in rats. Cardiovascular Pathology 12, 186-194CrossRef Google Scholar PubMed

82Szalay, G. et al. (2009) Osteopontin: a fibrosis-related marker molecule in cardiac remodeling of enterovirus myocarditis in the susceptible host. Circulation Research 104, 851-859CrossRef Google Scholar PubMed

83Makiishi-Shimobayashi, C. et al. (2004) Localization of osteopontin at calcification sites of cholesteatoma: possible role as a regulator of deposition of calcium phosphate in the middle ear. Auris, Nasus, Larynx 31, 3-9CrossRef Google Scholar PubMed

84Hikita, S.T. et al. (2006) Osteopontin is proinflammatory in experimental autoimmune uveitis. Investigative Ophthalmology and Visual Science 47, 4435-4443CrossRef Google Scholar PubMed

85Bosco, M.C. et al. (2009) The hypoxic synovial environment regulates expression of vascular endothelial growth factor and osteopontin in juvenile idiopathic arthritis. Journal of Rheumatology 36, 1318-1329CrossRef Google Scholar PubMed

86McKee, M.D. and Nanci, A. (1996) Secretion of osteopontin by macrophages and its accumulation at tissue surfaces during wound healing in mineralized tissues: a potential requirement for macrophage adhesion and phagocytosis. Anatomical Record 245, 394-4093.0.CO;2-K>CrossRef Google Scholar PubMed

87Mori, R., Shaw, T.J. and Martin, P. (2008) Molecular mechanisms linking wound inflammation and fibrosis: knockdown of osteopontin leads to rapid repair and reduced scarring. Journal of Experimental Medicine 205, 43-51Google Scholar

88Nakamura, M. et al. (2002) Osteopontin expression in chronic pancreatitis. Pancreas 25, 182-187CrossRef Google Scholar PubMed

89Sato, T. et al. (2005) Osteopontin/Eta-1 upregulated in Crohn's disease regulates the Th1 immune response. Gut 54, 1254-1262CrossRef Google Scholar PubMed

90White, F.J. et al. (2006) Secreted phosphoprotein 1 (osteopontin) is expressed by stromal macrophages in cyclic and pregnant endometrium of mice, but is induced by estrogen in luminal epithelium during conceptus attachment for implantation. Reproduction 132, 919-929Google Scholar

91Ophascharoensuk, V. et al. (1998) Role of intrinsic renal cells versus infiltrating cells in glomerular crescent formation. Kidney International 54, 416-425Google Scholar

92Hudkins, K.L. et al. (2000) Osteopontin expression in human crescentic glomerulonephritis. Kidney International 57, 105-116CrossRef Google Scholar PubMed

93Hartner, A. et al. (2001) Glomerular osteopontin expression and macrophage infiltration in glomerulosclerosis of DOCA-salt rats. American Journal of Kidney Diseases 38, 153-164CrossRef Google Scholar PubMed

94Hudkins, K.L. et al. (2001) Osteopontin expression in human cyclosporine toxicity. Kidney International 60, 635-640Google Scholar

95Cao, Z., Cox, A. and Bonnet, F. (2002) Increased osteopontin expression following renal ablation is attenuated by angiotensin type 1 receptor antagonism. Experimental Nephrology 10, 19-25CrossRef Google Scholar PubMed

96Tian, S. et al. (2006) Tubulointerstitial macrophage accumulation is regulated by sequentially expressed osteopontin and macrophage colony-stimulating factor: implication for the role of atorvastatin. Mediators of Inflammation 2006, 12919Google Scholar

97Peng, X. et al. (2006) Detection of osteopontin in the pericyst of human hepatic Echinococcus granulosus. Acta Tropica 100, 163-171Google Scholar

98Nishikaku, A.S. et al. (2009) Nitric oxide participation in granulomatous response induced by Paracoccidioides brasiliensis infection in mice. Medical Microbiology and Immunology 198, 123-135CrossRef Google Scholar PubMed

99Smith, L.L. et al. (1998) Osteopontin N-terminal domain contains a cryptic adhesive sequence recognized by à 9 á 1 integrin. Journal of Biological Chemistry 271, 28485-28491Google Scholar

100Kazanecki, C.C., Uzwiak, D.J. and Denhardt, D.T. (2007) Control of osteopontin signaling and function by post-translational phosphorylation and protein folding. Journal of Cellular Biochemistry 102, 912-924Google Scholar

101Prieto, J., Eklund, A. and Patarroyo, M. (1994) Regulated expression of integrins and other adhesion molecules during differentiation of monocytes into macrophages. Cellular Immunology 156, 191-211Google Scholar

102Ammon, C. et al. (2000) Comparative analysis of integrin expression on monocyte-derived macrophages and monocyte-derived dendritic cells. Immunology 100, 364-369CrossRef Google Scholar PubMed

103Shima, M. et al. (1995) Macrophage-colony-stimulating factor regulates expression of the integrins alpha 4 beta 1 and alpha 5 beta 1 by murine bone marrow macrophages. Proceedings of the National Academy of Sciences of the United States of America 92, 5179-5183CrossRef Google Scholar PubMed

104De Nichilo, M.O. and Burns, G.F. (1993) Granulocyte-macrophage and macrophage colony-stimulating factors differentially regulate alpha v integrin expression on cultured human macrophages. Proceedings of the National Academy of Sciences of the United States of America 90, 2517-2521Google Scholar

105Lacy-Hulbert, A. et al. (2007) Ulcerative colitis and autoimmunity induced by loss of myeloid alphav integrins. Proceedings of the National Academy of Sciences of the United States of America 104, 15823-15828CrossRef Google Scholar PubMed

106Ashkar, S. et al. (2000) Eta-1 (osteopontin): an early component of type-1 (cell-mediated) immunity. Science 287, 860-864Google Scholar

107Potter, M.R. et al. (2002) Role of osteopontin in murine Lyme arthritis and host defense against Borrelia burgdorferi. Infection and Immunity 70, 1372-1381Google Scholar

108Isoda, K. et al. (2003) Osteopontin transgenic mice fed a high-cholesterol diet develop early fatty-streak lesions. Circulation 107, 679-681CrossRef Google Scholar PubMed

109Abel, B. et al. (2005) Osteopontin is not required for the development of Th1 responses and viral immunity. Journal of Immunology 175, 6006-6013CrossRef Google Scholar

110O'Regan, A.W., Hayden, J.M. and Berman, J.S. (2000) Osteopontin augments CD3-mediated interferon-gamma and CD40 ligand expression by T cells, which results in IL-12 production from peripheral blood mononuclear cells. Journal of Leukocyte Biology 68, 495-502CrossRef Google Scholar

111Zhang, S. and Wang, Q. (2008) Factors determining the formation and release of bioactive IL-12: regulatory mechanisms for IL-12p70 synthesis and inhibition. Biochemical and Biophysical Research Communications 372, 509-512CrossRef Google Scholar PubMed

112Konno, S. et al. (2005) Endotoxin contamination contributes to the in vitro cytokine-inducing activity of osteopontin preparations. Journal of Interferon and Cytokine Research 25, 277-282Google Scholar

113Aziz, M. et al. (2009) MFG-E8 attenuates intestinal inflammation in murine experimental colitis by modulating osteopontin-dependent {alpha}v{beta}3 integrin signaling. Journal of Immunology 182, 7222-7232Google Scholar

114Shimizu, S. et al. (2010) Osteopontin deficiency impairs wear debris-induced osteolysis via regulation of cytokine secretion from murine macrophages. Arthritis and Rheumatism 62, 1329-1337CrossRef Google Scholar PubMed

115Naldini, A. et al. (2006) Cutting edge: IL-1beta mediates the proangiogenic activity of osteopontin-activated human monocytes. Journal of Immunology 177, 4267-4270Google Scholar

116Patarca, R., Saavedra, R.A. and Cantor, H. (1993) Molecular and cellular basis of genetic resistance to bacterial infection: the role of the early T-lymphocyte activation 1/ osteopontin gene. Critical Reviews in Immunology 13, 225-246Google Scholar PubMed

117Ono, M., Yamamoto, T. and Nose, M. (1995) Allelic difference in the nucleotide sequence of the Eta-1/Op gene transcript. Molecular Immunology 32, 447-448Google Scholar

118Miyazaki, T. et al. (2005) Implication of allelic polymorphism of osteopontin in the development of lupus nephritis in MRL/lpr mice. European Journal of Immunology 35, 1510-1520Google Scholar

119Gao, C. et al. (2003) Osteopontin inhibits expression of cytochrome c oxidase in RAW 264.7 murine macrophages. Biochemical and Biophysical Research Communications 309, 120-125Google Scholar

120Marroquin, C.E. et al. (2004) Osteopontin increases CD44 expression and cell adhesion in RAW 264.7 murine leukemia cells. Immunology Letters 95, 109-112CrossRef Google Scholar PubMed

121Vaschetto, R. et al. (2008) Serum levels of osteopontin are increased in SIRS and sepsis. Intensive Care Medicine 34, 2176-2184CrossRef Google Scholar PubMed

122Steitz, S.A. et al. (2002) Osteopontin inhibits mineral deposition and promotes regression of ectopic calcification. American Journal of Pathology 161, 2035-2046Google Scholar

123Rollo, E.E., Laskin, D.L. and Denhardt, D.T. (1996) Osteopontin inhibits nitric oxide production and cytotoxicity by activated RAW 264.7 macrophages. Journal of Leukocyte Biology 60, 397-404Google Scholar

124Tian, J.Y. et al. (2000) Regulation of NO synthesis induced by inflammatory mdiators in RAW264.7 cells: collagen prevents inhibition by osteopontin. Cytokine 12, 450-457Google Scholar

125Gao, C. et al. (2007) Osteopontin induces ubiquitin-dependent degradation of STAT1 in RAW264.7 murine macrophages. Journal of Immunology 178, 1870-1881CrossRef Google Scholar PubMed

126Guo, H. et al. (2008) Osteopontin mediates Stat1 degradation to inhibit iNOS transcription in a cecal ligation and puncture model of sepsis. Surgery 144, 182-188Google Scholar

127Bourassa, B., Monaghan, S. and Rittling, S.R. (2004) Impaired anti-tumor cytotoxicity of macrophages from osteopontin-deficient mice. Cellular Immunology 227, 1-11Google Scholar

128Heilmann, K. et al. (2009) Osteopontin as two-sided mediator of intestinal inflammation. Journal of Cellular and Molecular Medicine 13, 1162-1174Google Scholar

129Nau, G.J. et al. (1999) Attenuated host resistance against Mycobacterium bovis BCG infection in mice lacking osteopontin. Infection and Immunity 67, 4223-4230Google Scholar

130Pedraza, C.E. et al. (2008) Osteopontin functions as an opsonin and facilitates phagocytosis by macrophages of hydroxyapatite-coated microspheres: implications for bone wound healing. Bone 43, 708-716CrossRef Google Scholar PubMed

131Singh, R.P. et al. (1990) Definition of a specific interaction between the early T lymphocyte activation 1 (Eta-1) protein and murine macrophages in vitro and its effect upon macrophages in vivo. Journal of Experimental Medicine 171, 1931-1942CrossRef Google Scholar

132Giachelli, C.M. et al. (1998) Evidence for a role of osteopontin in macrophage infiltration in response to pathological stimuli in vivo. American Journal of Pathology 152, 353-358Google Scholar

133Marcondes, M.C. et al. (2008) In vivo osteopontin-induced macrophage accumulation is dependent on CD44 expression. Cellular Immunology 254, 56-62Google Scholar

134Bruemmer, D. et al. (2003) Angiotensin II-accelerated atherosclerosis and aneurysm formation is attenuated in osteopontin-deficient mice. Journal of Clinical Investigation 112, 1318-1331Google Scholar

135Duvall, C.L. et al. (2008) The role of osteopontin in recovery from hind limb ischemia. Arteriosclerosis, Thrombosis, and Vascular Biology 28, 290-295CrossRef Google Scholar PubMed

136Nystrom, T., Duner, P. and Hultgardh-Nilsson, A. (2007) A constitutive endogenous osteopontin production is important for macrophage function and differentiation. Experimental Cell Research 313, 1149-1160CrossRef Google Scholar PubMed

137Panzer, U. et al. (2001) Monocyte chemoattractant protein-1 and osteopontin differentially regulate monocytes recruitment in experimental glomerulonephritis. Kidney International 59, 1762-1769CrossRef Google Scholar PubMed

138Okada, H. et al. (2000) Osteopontin expressed by renal tubular epithelium mediates interstitial monocyte infiltration in rats. American Journal of Physiology. Renal Physiology 278, F110-F121Google Scholar

139Mazzali, M. et al. (2002) Effects of cyclosporine in osteopontin null mice. Kidney International 62, 78-85CrossRef Google Scholar PubMed

140Ophascharoensuk, V. et al. (1999) Obstructive uropathy in the mouse: role of osteopontin in interstitial fibrosis and apoptosis. Kidney International 56, 571-580Google Scholar

141Yoo, K.H. et al. (2006) Osteopontin regulates renal apoptosis and interstitial fibrosis in neonatal chronic unilateral ureteral obstruction. Kidney International 70, 1735-1741CrossRef Google Scholar PubMed

142Persy, V.P. et al. (2003) Reduced postischemic macrophage infiltration and interstitial fibrosis in osteopontin knockout mice. Kidney International 63, 543-553Google Scholar

143Wolak, T. et al. (2009) Osteopontin modulates angiotensin II-induced inflammation, oxidative stress, and fibrosis of the kidney. Kidney International 76, 32-43CrossRef Google Scholar PubMed

144Morimoto, J. et al. (2004) Osteopontin affects the persistence of beta-glucan-induced hepatic granuloma formation and tissue injury through two distinct mechanisms. International Immunology 16, 477-488Google Scholar

145O'Regan, A.W. et al. (2001) Abnormal pulmonary granuloma formation in osteopontin-deficient mice. American Journal of Respiratory and Critical Care Medicine 164, 2243-2247Google Scholar

146Crawford, H.C., Matrisian, L.M. and Liaw, L. (1998) Distinct roles of osteopontin in host defense activity and tumor survival during squamous cell carcinoma progression in vivo. Cancer Research 58, 5206-5215Google Scholar PubMed

147Feng, F. and Rittling, S.R. (2000) Mammary tumor development in MMTV-c-myc/MMTV-v-Ha-ras transgenic mice is unaffected by osteopontin deficiency. Breast Cancer Research and Treatment 63, 71-79Google Scholar

148Cheng, J. et al. (2007) Human macrophages promote the motility and invasiveness of osteopontin-knockdown tumor cells. Cancer Research 67, 5141-5147CrossRef Google Scholar PubMed

149Kiefer, F.W. et al. (2010) Neutralization of osteopontin inhibits obesity-induced inflammation and insulin resistance. Diabetes 59, 935-946Google Scholar

150Kwon, H.J. et al. (2010) The role of osteopontin in d-galactosamine-induced liver injury in genetically obese mice. Toxicology and Applied Pharmacology 242, 344-351Google Scholar

151da Silva, A.P. et al. (2009) Osteopontin attenuation of dextran sulfate sodium-induced colitis in mice. Lab Investigation 89, 1169-1181CrossRef Google Scholar PubMed

152da Silva, A.P. et al. (2006) Exacerbated tissue destruction in DSS-induced acute colitis of OPN-null mice is associated with downregulation of TNF-alpha expression and non-programmed cell death. Journal of Cellular Physiology 208, 629-639CrossRef Google Scholar PubMed

153Zhong, J. et al. (2006) Osteopontin deficiency protects mice from Dextran sodium sulfate-induced colitis. Inflammatory Bowel Diseases 12, 790-796CrossRef Google Scholar PubMed

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Osteopontin in macrophage function

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Osteopontin in macrophage function

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