Abstract
The aim of this study was to investigate the cellular and molecular expression of tartrate resistant acid phosphatase (TRAP) as a marker of activated macrophages in macrophage dependent dextran sulphate sodium (DSS)-induced colitis in rats. In normal colon, TRAP+/CX3CR1+ macrophages were located in the upper part of the lamina propria. In the early stage (day 1–3) of acute colitis prior to histopathological changes, induction of the cytokines TNFα, IL-12 and IFNγ occurred concomitant with increased mRNA and enzyme activity of TRAP along with a slight increase of TRAP immunolabelling in macrophages of the upper lamina propria, suggesting induction of TRAP in resident macrophages. Among these cytokines, TNFα up-regulated TRAP expression in the RAW 264.7 monocyte/macrophage cell line. In a later phase (day 7) with fulminant colitis, a massive infiltration of macrophages including recruited TRAP+/CCR2+ cells was observed also in the lower part of the lamina propria as well as in the submuscular layer. Additionally, differentiated cellular expression of pro- and mature TRAP also suggest that mucosal macrophages in the lower part of lamina propria bordering the sub-mucosa provide a source of replenishment of macrophages situated in the upper lamina propria. In conclusion, induction of TRAP provides an early sign of macrophage responsiveness in DSS induced colitis.
Similar content being viewed by others
References
Andersson G, Ek-Rylander B, Hollberg K, Ljusberg-Sjolander J, Lang P, Norgard M, Wang Y, Zhang SJ (2003) TRACP as an osteopontin phosphatase. J Bone Miner Res 18:1912–1915
Andres PG, Beck PL, Mizoguchi E, Mizoguchi A, Bhan AK, Dawson T, Kuziel WA, Maeda N, MacDermott RP, Podolsky DK, Reinecker HC (2000) Mice with a selective deletion of the CC chemokine receptors 5 or 2 are protected from dextran sodium sulfate-mediated colitis: lack of CC chemokine receptor 5 expression results in a NK1.1+ lymphocyte-associated Th2-type immune response in the intestine. J Immunol 164:6303–6312
Ashkar S, Weber GF, Panoutsakopoulou V, Sanchirico ME, Jansson M, Zawaideh S, Rittling SR, Denhardt DT, Glimcher MJ, Cantor H (2000) Eta-1 (osteopontin): an early component of type-1 (cell-mediated) immunity. Science 287:860–864
Axelsson LG, Landstrom E, Goldschmidt TJ, Gronberg A, Bylund-Fellenius AC (1996) Dextran sulfate sodium (DSS) induced experimental colitis in immunodeficient mice: effects in CD4(+)-cell depleted, athymic and NK-cell depleted SCID mice. Inflamm Res 45:181–191
Bernstein CN, Sargent M, Leslie WD (2005) Serum osteoprotegerin is increased in Crohn’s disease: a population-based case control study. Inflamm Bowel Dis 11:325–330
Bune AJ, Hayman AR, Evans MJ, Cox TM (2001) Mice lacking tartrate-resistant acid phosphatase (Acp 5) have disordered macrophage inflammatory responses and reduced clearance of the pathogen, Staphylococcus aureus. Immunology 102:103–113
Cario E, Podolsky DK (2000) Differential alteration in intestinal epithelial cell expression of toll-like receptor 3 (TLR3) and TLR4 in inflammatory bowel disease. Infect Immun 68:7010–7017
Cooper HS, Murthy SN, Shah RS, Sedergran DJ (1993) Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest 69:238–249
Dieleman LA, Ridwan BU, Tennyson GS, Beagley KW, Bucy RP, Elson CO (1994) Dextran sulfate sodium-induced colitis occurs in severe combined immunodeficient mice. Gastroenterology 107:1643–1652
Dieleman LA, Palmen MJ, Akol H, Bloemena E, Pena AS, Meuwissen SG, Van Rees EP (1998) Chronic experimental colitis induced by dextran sulphate sodium (DSS) is characterized by Th1 and Th2 cytokines. Clin Exp Immunol 114:385–391
Dionne S, Hiscott J, D’Agata I, Duhaime A, Seidman EG (1997) Quantitative PCR analysis of TNF-alpha and IL-1 beta mRNA levels in pediatric IBD mucosal biopsies. Dig Dis Sci 42:1557–1566
Egger B, Bajaj-Elliott M, MacDonald TT, Inglin R, Eysselein VE, Buchler MW (2000) Characterisation of acute murine dextran sodium sulphate colitis: cytokine profile and dose dependency. Digestion 62:240–248
Ek-Rylander B, Bill P, Norgård M, Nilsson S, Andersson G (1991) Cloning, sequence, and developmental expression of a type 5, tartrate-resistant, acid phosphatase of rat bone. J Biol Chem 266:24684–24689
Ek-Rylander B, Flores M, Wendel M, Heinegard D, Andersson G (1994) Dephosphorylation of osteopontin and bone sialoprotein by osteoclastic tartrate-resistant acid phosphatase. Modulation of osteoclast adhesion in vitro. J Biol Chem 269:14853–14856
Ek-Rylander B, Barkhem T, Ljusberg J, Ohman L, Andersson KK, Andersson G (1997) Comparative studies of rat recombinant purple acid phosphatase and bone tartrate-resistant acid phosphatase. Biochem J 321(Pt 2):305–311
Fuss IJ, Neurath M, Boirivant M, Klein JS, de la Motte C, Strong SA, Fiocchi C, Strober W (1996) Disparate CD4+ lamina propria (LP) lymphokine secretion profiles in inflammatory bowel disease. Crohn’s disease LP cells manifest increased secretion of IFN-gamma, whereas ulcerative colitis LP cells manifest increased secretion of IL-5. J Immunol 157:1261–1270
Fuss IJ, Becker C, Yang Z, Groden C, Hornung RL, Heller F, Neurath MF, Strober W, Mannon PJ (2006) Both IL-12p70 and IL-23 are synthesized during active Crohn’s disease and are down-regulated by treatment with anti-IL-12 p40 monoclonal antibody. Inflamm Bowel Dis 12:9–15
Gaudio E, Taddei G, Vetuschi A, Sferra R, Frieri G, Ricciardi G, Caprilli R (1999) Dextran sulfate sodium (DSS) colitis in rats: clinical, structural, and ultrastructural aspects. Dig Dis Sci 44:1458–1475
Hart AL, Al-Hassi HO, Rigby RJ, Bell SJ, Emmanuel AV, Knight SC, Kamm MA, Stagg AJ (2005) Characteristics of intestinal dendritic cells in inflammatory bowel diseases. Gastroenterology 129:50–65
Hayman A, Bune A, Bradley J, Rashbass J, Cox T (2000) Osteoclastic tartrate-resistant acid phophatase (Acp 5): its to dendritic cells and diverse murine tissues. J Histochem Cytochem 48:219–228
Hayman AR, Macary P, Lehner PJ, Cox TM (2001) Tartrate-resistant acid phosphatase (Acp 5): identification in diverse human tissues and dendritic cells. J Histochem Cytochem 49:675–684
Ina K, Itoh J, Fukushima K, Kusugami K, Yamaguchi T, Kyokane K, Imada A, Binion DG, Musso A, West GA, Dobrea GM, McCormick TS, Lapetina EG, Levine AD, Ottaway CA, Fiocchi C (1999) Resistance of Crohn’s disease T cells to multiple apoptotic signals is associated with a Bcl-2/Bax mucosal imbalance. J Immunol 163:1081–1090
Irvine EJ, Marshall JK (2000) Increased intestinal permeability precedes the onset of Crohn’s disease in a subject with familial risk. Gastroenterology 119:1740–1744
Janckila AJ, Slone SP, Lear SC, Martin A, Yam LT (2007) Tartrate-resistant acid phosphatase as an immunohistochemical marker for inflammatory macrophages. Am J Clin Pathol 127:556–566
Lång P, Andersson G (2005) Differential expression of monomeric and proteolytically processed forms of tartrate-resistant acid phosphatase in rat tissues. Cell Mol Life Sci 62:905–918
Lång P, Schultzberg M, Andersson G (2001) Expression and distribution of tartrate-resistant purple acid phosphatase in the rat nervous system. J Histochem Cytochem 49:379–396
Langrish CL, Chen Y, Blumenschein WM, Mattson J, Basham B, Sedgwick JD, McClanahan T, Kastelein RA, Cua DJ (2005) IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med 201:233–240
Leon F, Smythies LE, Smith PD, Kelsall BL (2006) Involvement of dendritic cells in the pathogenesis of inflammatory bowel disease. Adv Exp Med Biol 579:117–132
Leung FW, Heng MC, Allen S, Seno K, Leung JW, Heng MK (2000) Involvement of luminal bacteria, heat shock protein 60, macrophages and gammadelta T cells in dextran sulfate sodium-induced colitis in rats. Dig Dis Sci 45:1472–1479
Ljusberg J, Wang Y, Lang P, Norgard M, Dodds R, Hultenby K, Ek-Rylander B, Andersson G (2005) Proteolytic excision of a repressive loop domain in tartrate-resistant acid phosphatase by cathepsin K in osteoclasts. J Biol Chem 280:28370–28381
MacDonald TT, Monteleone G (2001) IL-12 and Th1 immune responses in human Peyer’s patches. Trends Immunol 22:244–247
Mahler M, Bristol IJ, Leiter EH, Workman AE, Birkenmeier EH, Elson CO, Sundberg JP (1998) Differential susceptibility of inbred mouse strains to dextran sulfate sodium-induced colitis. Am J Physiol 274:G544–G551
Martin B, Banz A, Bienvenu B, Cordier C, Dautigny N, Becourt C, Lucas B (2004) Suppression of CD4+ T lymphocyte effector functions by CD4+ CD25+ cells in vivo. J Immunol 172:3391–3398
Morise K, Yamaguchi T, Kuroiwa A, Kanayama K, Matsuura T, Shinoda M, Yamamoto H, Horiuchi Y, Furusawa A, Iwase H et al (1994) Expression of adhesion molecules and HLA-DR by macrophages and dendritic cells in aphthoid lesions of Crohn’s disease: an immunocytochemical study. J Gastroenterol 29:257–264
Moschen AR, Kaser A, Enrich B, Ludwiczek O, Gabriel M, Obrist P, Wolf AM, Tilg H (2005) The RANKL/OPG system is activated in inflammatory bowel disease and relates to the state of bone loss. Gut 54:479–487
Muhonen P, Avnet S, Parthasarathy RN, Janckila AJ, Halleen JM, Laitala-Leinonen T, Vaananen HK (2007) Sequence and TLR9 independent increase of TRACP expression by antisense DNA and siRNA molecules. Biochem Biophys Res Commun 359(4):889–895
Nagashima R, Maeda K, Imai Y, Takahashi T (1996) Lamina propria macrophages in the human gastrointestinal mucosa: their distribution, immunohistological phenotype, and function. J Histochem Cytochem 44:721–731
Ni J, Chen SF, Hollander D (1996) Effects of dextran sulphate sodium on intestinal epithelial cells and intestinal lymphocytes. Gut 39:234–241
Ohkawara T, Nishihira J, Ishiguro Y, Otsubo E, Nagai K, Takeda H, Kato M, Yoshiki T, Iwanaga T, Asaka M (2006) Resistance to experimental colitis depends on cytoprotective heat shock proteins in macrophage migration inhibitory factor null mice. Immunol Lett 107:148–154
Ohkawara T, Mitsuyama K, Takeda H, Asaka M, Fujiyama Y, Nishihira J (2008) Lack of macrophage migration inhibitory factor suppresses innate immune response in murine dextran sulfate sodium-induced colitis. Scand J Gastroenterol 43(12):1497–1504
Okayasu I, Hatakeyama S, Yamada M, Ohkusa T, Inagaki Y, Nakaya R (1990) A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterology 98:694–702
Raisanen SR, Halleen J, Parikka V, Vaananen HK (2001) Tartrate-resistant acid phosphatase facilitates hydroxyl radical formation and colocalizes with phagocytosed Staphylococcus aureus in alveolar macrophages. Biochem Biophys Res Commun 288:142–150
Raisanen SR, Alatalo SL, Ylipahkala H, Halleen JM, Cassady AI, Hume DA, Vaananen HK (2005) Macrophages overexpressing tartrate-resistant acid phosphatase show altered profile of free radical production and enhanced capacity of bacterial killing. Biochem Biophys Res Commun 331:120–126
Reed KL, Fruin AB, Gower AC, Gonzales KD, Stucchi AF, Andry CD, O’Brien M, Becker JM (2005) NF-kappaB activation precedes increases in mRNA encoding neurokinin-1 receptor, proinflammatory cytokines, and adhesion molecules in dextran sulfate sodium-induced colitis in rats. Dig Dis Sci 50:2366–2378
Rogler G, Hausmann M, Spottl T, Vogl D, Aschenbrenner E, Andus T, Falk W, Scholmerich J, Gross V (1999) T-cell co-stimulatory molecules are upregulated on intestinal macrophages from inflammatory bowel disease mucosa. Eur J Gastroenterol Hepatol 11:1105–1111
Sasaki Y, Tanaka M, Kudo H (2002) Differentiation between ulcerative colitis and Crohn’s disease by a quantitative immunohistochemical evaluation of T lymphocytes, neutrophils, histiocytes and mast cells. Pathol Int 52:277–285
Sato T, Nakai T, Tamura N, Okamoto S, Matsuoka K, Sakuraba A, Fukushima T, Uede T, Hibi T (2005) Osteopontin/Eta-1 upregulated in Crohn’s disease regulates the Th1 immune response. Gut 54:1254–1262
Shintani N, Nakajima T, Okamoto T, Kondo T, Nakamura N, Mayumi T (1998) Involvement of CD4+ T cells in the development of dextran sulfate sodium-induced experimental colitis and suppressive effect of IgG on their action. Gen Pharmacol 31:477–481
Sivakumar PV, Westrich GM, Kanaly S, Garka K, Born TL, Derry JM, Viney JL (2002) Interleukin 18 is a primary mediator of the inflammation associated with dextran sulphate sodium induced colitis: blocking interleukin 18 attenuates intestinal damage. Gut 50:812–820
Smith PD, Ochsenbauer-Jambor C, Smythies LE (2005) Intestinal macrophages: unique effector cells of the innate immune system. Immunol Rev 206:149–159
Soderholm JD, Olaison G, Peterson KH, Franzen LE, Lindmark T, Wiren M, Tagesson C, Sjodahl R (2002) Augmented increase in tight junction permeability by luminal stimuli in the non-inflamed ileum of Crohn’s disease. Gut 50:307–313
Sund M, Xu LL, Rahman A, Qian BF, Hammarstrom ML, Danielsson A (2005) Reduced susceptibility to dextran sulphate sodium-induced colitis in the interleukin-2 heterozygous (IL-2) mouse. Immunology 114:554–564
te Velde AA, de Kort F, Sterrenburg E, Pronk I, ten Kate FJ, Hommes DW, van Deventer SJ (2007) Comparative analysis of colonic gene expression of three experimental colitis models mimicking inflammatory bowel disease. Inflamm Bowel Dis 13:325–330
Togawa J, Nagase H, Tanaka K, Inamori M, Nakajima A, Ueno N, Saito T, Sekihara H (2002) Oral administration of lactoferrin reduces colitis in rats via modulation of the immune system and correction of cytokine imbalance. J Gastroenterol Hepatol 17:1291–1298
Trinchieri G (2003) Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat Rev Immunol 3:133–146
Van den Brande JM, Braat H, van den Brink GR, Versteeg HH, Bauer CA, Hoedemaeker I, van Montfrans C, Hommes DW, Peppelenbosch MP, van Deventer SJ (2003) Infliximab but not etanercept induces apoptosis in lamina propria T-lymphocytes from patients with Crohn’s disease. Gastroenterology 124:1774–1785
Wang Y, Andersson G (2007) Expression and proteolytic processing of mammalian purple acid phosphatase in CHO-K1 cells. Arch Biochem Biophys 461:85–94
Yoshihara K, Yajima T, Kubo C, Yoshikai Y (2006) Role of interleukin 15 in colitis induced by dextran sulphate sodium in mice. Gut 55:334–341
Acknowledgments
This study was supported by grants from the Swedish Research Council, Karolinska Institutet, Stockholm County Council, University of Kalmar, The Lua- ALF agreement, the Anna-Lisa and Bror Björnsson Foundation and the Magnus Bergvall foundation.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lång, P., Lange, S., Delbro, D. et al. Induction and cellular expression of tartrate resistant acid phosphatase during dextran sodium sulphate induced colitis in rats. Histochem Cell Biol 132, 599–612 (2009). https://doi.org/10.1007/s00418-009-0647-4
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00418-009-0647-4