Top

Published in:

01-10-2012 | Original Article

Phenotypic change of macrophages in the progression of diabetic nephropathy; sialoadhesin-positive activated macrophages are increased in diabetic kidney

Authors: Ryo Nagase, Nobuo Kajitani, Kenichi Shikata, Daisuke Ogawa, Ryo Kodera, Shinichi Okada, Yuichi Kido, Hirofumi Makino

Published in: Clinical and Experimental Nephrology | Issue 5/2012

Abstract

Background

Inflammatory process is involved in pathogenesis of diabetic nephropathy, although the activation and phenotypic change of macrophages in diabetic kidney has remained unclear. Sialoadhesin is a macrophage adhesion molecule containing 17 extracellular immunoglobulin-like domains, and is an I-type lectin which binds to sialic acid ligands expressed on hematopoietic cells. The aim of this study is to clarify the activation and phenotypic change of macrophages in the progression of diabetic nephropathy.

Methods

We examined the expression of surface markers for pan-macrophages, resident macrophages, sialoadhesin, major histocompatibility complex class II and α-smooth muscle actin in the glomeruli of diabetic rats using immunohistochemistry at 0, 1, 4, 12, and 24 weeks after induction of diabetes by streptozotocin. Expression of type IV collagen and the change of mesangial matrix area were also measured. The mechanism for up-regulated expression of sialoadhesin on macrophages was evaluated in vitro.

Results

The number of macrophages was increased in diabetic glomeruli at 1 month after induction of diabetes and the increased number was maintained until 6 months. On the other hand, sialoadhesin-positive macrophages were increased during the late stage of diabetes concomitantly with the increase of α-smooth muscle actin-positive mesangial cells, mesangial matrix area and type IV collagen. Gene expression of sialoadhesin was induced by stimulation with interleukin (IL)-1β and tumor necrosis factor-α but not with IL-4, transforming growth factor-β and high glucose in cultured human macrophages.

Conclusion

The present findings suggest that sialoadhesin-positive macrophages may contribute to the progression of diabetic nephropathy.

Furuta T, Saito T, Ootaka T, Soma J, Obara K, Abe K, et al. The role of macrophages in diabetic glomerulosclerosis. Am J Kidney Dis. 1993;21(5):480–5.PubMed

Sugimoto H, Shikata K, Hirata K, Akiyama K, Matsuda M, Kushiro M, et al. Increased expression of intercellular adhesion molecule-1 (ICAM-1) in diabetic rat glomeruli: glomerular hyperfiltration is a potential mechanism of ICAM-1 upregulation. Diabetes. 1997;46(12):2075–81.PubMedCrossRef

Okada S, Shikata K, Matsuda M, Ogawa D, Usui H, Kido Y, et al. Intercellular adhesion molecule-1-deficient mice are resistant against renal injury after induction of diabetes. Diabetes. 2003;52(10):2586–93.PubMedCrossRef

Crocker PR, Gordon S. Properties and distribution of a lectin-like hemagglutinin differentially expressed by murine stromal tissue macrophages. J Exp Med. 1986;164(6):1862–75.PubMedCrossRef

Crocker PR, Gordon S. Mouse macrophage hemagglutinin (sheep erythrocyte receptor) with specificity for sialylated glycoconjugates characterized by a monoclonal antibody. J Exp Med. 1989;169(4):1333–46.PubMedCrossRef

Crocker PR, Hill M, Gordon S. Regulation of a murine macrophage haemagglutinin (sheep erythrocyte receptor) by a species-restricted serum factor. Immunology. 1988;65(4):515–22.PubMed

van den Berg TK, van Die I, de Lavalette CR, Dopp EA, Smit LD, van der Meide PH, et al. Regulation of sialoadhesin expression on rat macrophages. Induction by glucocorticoids and enhancement by IFN-beta, IFN-gamma, IL-4, and lipopolysaccharide. J Immunol. 1996;157(7):3130–8.PubMed

Steiniger B, Barth P, Herbst B, Hartnell A, Crocker PR. The species-specific structure of microanatomical compartments in the human spleen: strongly sialoadhesin-positive macrophages occur in the perifollicular zone, but not in the marginal zone. Immunology. 1997;92(2):307–16.PubMedCrossRef

Ito Y, Kawachi H, Morioka Y, Nakatsue T, Koike H, Ikezumi Y, et al. Fractalkine expression and the recruitment of CX3CR1+ cells in the prolonged mesangial proliferative glomerulonephritis. Kidney Int. 2002;61(6):2044–57.PubMedCrossRef

10.

Lan HY, Nikolic-Paterson DJ, Mu W, Atkins RC. Local macrophage proliferation in the progression of glomerular and tubulointerstitial injury in rat anti-GBM glomerulonephritis. Kidney Int. 1995;48(3):753–60.PubMedCrossRef

11.

Lai PC, Cook HT, Smith J, Keith JC Jr, Pusey CD, Tam FW. Interleukin-11 attenuates nephrotoxic nephritis in Wistar Kyoto rats. J Am Soc Nephrol. 2001;12(11):2310–20.PubMed

12.

Ikezumi Y, Kanno K, Karasawa T, Han GD, Ito Y, Koike H, et al. The role of lymphocytes in the experimental progressive glomerulonephritis. Kidney Int. 2004;66(3):1036–48.PubMedCrossRef

13.

Dijkstra CD, Dopp EA, Joling P, Kraal G. The heterogeneity of mononuclear phagocytes in lymphoid organs: distinct macrophage subpopulations in the rat recognized by monoclonal antibodies ED1, ED2 and ED3. Immunology. 1985;54(3):589–99.PubMed

14.

Mauer SM, Steffes MW, Ellis EN, Sutherland DE, Brown DM, Goetz FC. Structural-functional relationships in diabetic nephropathy. J Clin Invest. 1984;74(4):1143–55.PubMedCrossRef

15.

Osterby R, Parving HH, Hommel E, Jorgensen HE, Lokkegaard H. Glomerular structure and function in diabetic nephropathy. Early to advanced stages. Diabetes. 1990;39(9):1057–63.PubMedCrossRef

16.

Makino H, Yamasaki Y, Hironaka K, Ota Z. Glomerular extracellular matrices in rat diabetic glomerulopathy by scanning electron microscopy. Virchows Arch B Cell Pathol Incl Mol Pathol. 1992;62(1):19–24.PubMedCrossRef

17.

Makino H, Yamasaki Y, Haramoto T, Shikata K, Hironaka K, Ota Z, et al. Ultrastructural changes of extracellular matrices in diabetic nephropathy revealed by high resolution scanning and immunoelectron microscopy. Lab Invest. 1993;68(1):45–55.PubMed

18.

Abrass CK, Peterson CV, Raugi GJ. Phenotypic expression of collagen types in mesangial matrix of diabetic and nondiabetic rats. Diabetes. 1988;37(12):1695–702.PubMedCrossRef

19.

Makino H, Shikata K, Wieslander J, Wada J, Kashihara N, Yoshioka K, et al. Localization of fibril/microfibril and basement membrane collagens in diabetic glomerulosclerosis in type 2 diabetes. Diabet Med. 1994;11(3):304–11.PubMedCrossRef

20.

Johnson RJ, Iida H, Alpers CE, Majesky MW, Schwartz SM, Pritzi P, et al. Expression of smooth muscle cell phenotype by rat mesangial cells in immune complex nephritis. Alpha-smooth muscle actin is a marker of mesangial cell proliferation. J Clin Invest. 1991;87(3):847–58.PubMedCrossRef

21.

Alpers CE, Hudkins KL, Gown AM, Johnson RJ. Enhanced expression of “muscle-specific” actin in glomerulonephritis. Kidney Int. 1992;41(5):1134–42.PubMedCrossRef

22.

Kodera R, Shikata K, Kataoka HU, Takatsuka T, Miyamoto S, Sasaki M, et al. Glucagon-like peptide-1 receptor agonist ameliorates renal injury through its anti-inflammatory action without lowering blood glucose level in a rat model of type 1 diabetes. Diabetologia. 2011;54(4):965–78.PubMedCrossRef

23.

Takeya M, Hsiao L, Takahashi K. A new monoclonal antibody, TRPM-3, binds specifically to certain rat macrophage populations: immunohistochemical and immunoelectron microscopic analysis. J Leukoc Biol. 1987;41(3):187–95.PubMed

24.

Crocker PR, Mucklow S, Bouckson V, McWilliam A, Willis AC, Gordon S, et al. Sialoadhesin, a macrophage sialic acid binding receptor for haemopoietic cells with 17 immunoglobulin-like domains. EMBO J. 1994;13(19):4490–503.PubMed

25.

Hartnell A, Steel J, Turley H, Jones M, Jackson DG, Crocker PR. Characterization of human sialoadhesin, a sialic acid binding receptor expressed by resident and inflammatory macrophage populations. Blood. 2001;97(1):288–96.PubMedCrossRef

26.

Crocker PR, Varki A. Siglecs, sialic acids and innate immunity. Trends Immunol. 2001;22(6):337–42.PubMedCrossRef

27.

Crocker PR, Hartnell A, Munday J, Nath D. The potential role of sialoadhesin as a macrophage recognition molecule in health and disease. Glycoconj J. 1997;14(5):601–9.PubMedCrossRef

28.

Wiseman MJ, Viberti GC, Keen H. Threshold effect of plasma glucose in the glomerular hyperfiltration of diabetes. Nephron. 1984;38(4):257–60.PubMedCrossRef

29.

Osterby R, Gundersen HJ. Fast accumulation of basement membrane material and the rate of morphological changes in acute experimental diabetic glomerular hypertrophy. Diabetologia. 1980;18(6):493–500.PubMedCrossRef

30.

Harris RC, Haralson MA, Badr KF. Continuous stretch-relaxation in culture alters rat mesangial cell morphology, growth characteristics, and metabolic activity. Lab Invest. 1992;66(5):548–54.PubMed

31.

Miyatake N, Shikata K, Wada J, Sugimoto H, Takahashi S, Makino H. Differential distribution of insulin-like growth factor-1 and insulin-like growth factor binding proteins in experimental diabetic rat kidney. Nephron. 1999;81(3):317–23.PubMedCrossRef

32.

Floege J, Topley N, Hoppe J, Barrett TB, Resch K. Mitogenic effect of platelet-derived growth factor in human glomerular mesangial cells: modulation and/or suppression by inflammatory cytokines. Clin Exp Immunol. 1991;86(2):334–41.PubMedCrossRef

33.

Fukui M, Nakamura T, Ebihara I, Makita Y, Osada S, Tomino Y, et al. Effects of enalapril on endothelin-1 and growth factor gene expression in diabetic rat glomeruli. J Lab Clin Med. 1994;123(5):763–8.PubMed

34.

Shimokado K, Raines EW, Madtes DK, Barrett TB, Benditt EP, Ross R. A significant part of macrophage-derived growth factor consists of at least two forms of PDGF. Cell. 1985;43(1):277–86.PubMedCrossRef

35.

Ross R, Raines EW, Bowen-Pope DF. The biology of platelet-derived growth factor. Cell. 1986;46(2):155–69.PubMedCrossRef

Title: Phenotypic change of macrophages in the progression of diabetic nephropathy; sialoadhesin-positive activated macrophages are increased in diabetic kidney
Authors: Ryo Nagase
Nobuo Kajitani
Kenichi Shikata
Daisuke Ogawa
Ryo Kodera
Shinichi Okada
Yuichi Kido
Hirofumi Makino
Publication date: 01-10-2012
Publisher: Springer Japan
Published in: Clinical and Experimental Nephrology / Issue 5/2012
Print ISSN: 1342-1751
Electronic ISSN: 1437-7799
DOI: https://doi.org/10.1007/s10157-012-0625-3

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 5/2012

Relationship between renal hemodynamic status and aging in patients without diabetes evaluated by renal Doppler ultrasonography

Serum levels of soluble secreted α-Klotho are decreased in the early stages of chronic kidney disease, making it a probable novel biomarker for early diagnosis

The elevation of oxidative stress after the great East Japan earthquake

The complex of immunoglobulin A and uromodulin as a diagnostic marker for immunoglobulin A nephropathy

Mizoribine, tacrolimus, and corticosteroid combination therapy successfully induces remission in patients with lupus nephritis

A case of adefovir-induced membranous nephropathy related to hepatitis B caused by lamivudine-resistant virus after liver transplant due to Byler’s disease

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials