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Published in: European Journal of Applied Physiology 5/2013

01-05-2013 | Original Article

Circulating MMP-9 during exercise in humans

Authors: E. Rullman, K. Olsson, D. Wågsäter, T. Gustafsson

Published in: European Journal of Applied Physiology | Issue 5/2013

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Abstract

Matrix metalloproteinase 9 (MMP-9) is a member of a family of zinc-dependent endopeptidases capable of degrading extracellular matrix (ECM) proteins. A single bout of exercise increases levels of activated MMP-9 in skeletal muscle and in the circulation. However, whether the exercise-induced activation of MMP-9 is associated with ECM remodeling and the cellular source behind MMP-9 in the circulation is not known. In the present study ten healthy male subjects performed a single cycle exercise bout and arterial and venous femoral blood was collected. To test if exercise induces basal lamina degradation and if circulating levels of MMP-9 is related to a release from the exercising muscle, arteriovenous differences of collagen IV and MMP-9 were measured by ELISA and zymography, respectively. Furthermore, markers of neutrophil degranulation elastase and neutrophil gelatinase-associated lipocalin (NGAL) were measured by ELISA. Plasma levels of collagen IV increased during the exercise bout and an increased arteriovenous difference of collagen IV was noted at 27 min of exercise. Plasma levels of MMP-9 were increased at both 27 and 57 min of exercise but no arteriovenous difference was noted. No changes over time were detected for elastase and NGAL. The observed release of collagen IV from the exercising muscle indicate basal lamina turnover following a single bout of exercise. No detectable release of MMP-9 was observed, suggesting that the increase in plasma MMP-9 could come from a source other than the skeletal muscle.
Literature
go back to reference Akira S, Kishimoto T (1996) Role of interleukin-6 in macrophage function. Curr Opin Hematol 3:87–93PubMedCrossRef Akira S, Kishimoto T (1996) Role of interleukin-6 in macrophage function. Curr Opin Hematol 3:87–93PubMedCrossRef
go back to reference Axelsson L, Bergenfeldt M, Ohlsson K (1995) Studies of the release and turnover of a human neutrophil lipocalin. Scand J Clin Lab Invest 55:577–588PubMedCrossRef Axelsson L, Bergenfeldt M, Ohlsson K (1995) Studies of the release and turnover of a human neutrophil lipocalin. Scand J Clin Lab Invest 55:577–588PubMedCrossRef
go back to reference Bergers G, Brekken R, McMahon G, Vu TH, Itoh T, Tamaki K, Tanzawa K, Thorpe P, Itohara S, Werb Z, Hanahan D (2000) Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nat Cell Biol 2:737–744PubMedCrossRef Bergers G, Brekken R, McMahon G, Vu TH, Itoh T, Tamaki K, Tanzawa K, Thorpe P, Itohara S, Werb Z, Hanahan D (2000) Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nat Cell Biol 2:737–744PubMedCrossRef
go back to reference Büttner P, Mosig S, Lechtermann A, Funke H, Mooren FC (2007) Exercise affects the gene expression profiles of human white blood cells. J Appl Physiol 102:26–36PubMedCrossRef Büttner P, Mosig S, Lechtermann A, Funke H, Mooren FC (2007) Exercise affects the gene expression profiles of human white blood cells. J Appl Physiol 102:26–36PubMedCrossRef
go back to reference Chakrabarti S, Zee JM, Patel KD (2006) Regulation of matrix metalloproteinase-9 (MMP-9) in TNF-stimulated neutrophils: novel pathways for tertiary granule release. J Leukoc Biol 79:214–222PubMedCrossRef Chakrabarti S, Zee JM, Patel KD (2006) Regulation of matrix metalloproteinase-9 (MMP-9) in TNF-stimulated neutrophils: novel pathways for tertiary granule release. J Leukoc Biol 79:214–222PubMedCrossRef
go back to reference Clahsen T, Schaper F (2008) Interleukin-6 acts in the fashion of a classical chemokine on monocytic cells by inducing integrin activation, cell adhesion, actin polymerization, chemotaxis, and transmigration. J Leukoc Biol 84:1521–1529PubMedCrossRef Clahsen T, Schaper F (2008) Interleukin-6 acts in the fashion of a classical chemokine on monocytic cells by inducing integrin activation, cell adhesion, actin polymerization, chemotaxis, and transmigration. J Leukoc Biol 84:1521–1529PubMedCrossRef
go back to reference Coppock HA, White A, Aplin JD, Westwood M (2004) Matrix metalloprotease-3 and -9 proteolyze insulin-like growth factor-binding protein-1. Biol Reprod 71:438–443PubMedCrossRef Coppock HA, White A, Aplin JD, Westwood M (2004) Matrix metalloprotease-3 and -9 proteolyze insulin-like growth factor-binding protein-1. Biol Reprod 71:438–443PubMedCrossRef
go back to reference Cowland JB, Borregaard N (1999) The individual regulation of granule protein mRNA levels during neutrophil maturation explains the heterogeneity of neutrophil granules. J Leukoc Biol 66:989–995PubMed Cowland JB, Borregaard N (1999) The individual regulation of granule protein mRNA levels during neutrophil maturation explains the heterogeneity of neutrophil granules. J Leukoc Biol 66:989–995PubMed
go back to reference Haas TL, Milkiewicz M, Davis SJ, Zhou AL, Egginton S, Brown MD, Madri JA, Hudlicka O (2000) Matrix metalloproteinase activity is required for activity-induced angiogenesis in rat skeletal muscle. Am J Physiol 279:H1540–H1547 Haas TL, Milkiewicz M, Davis SJ, Zhou AL, Egginton S, Brown MD, Madri JA, Hudlicka O (2000) Matrix metalloproteinase activity is required for activity-induced angiogenesis in rat skeletal muscle. Am J Physiol 279:H1540–H1547
go back to reference Heinemeier KM, Olesen JL, Haddad F, Langberg H, Kjaer M, Baldwin KM, Schjerling P (2007) Expression of collagen and related growth factors in rat tendon and skeletal muscle in response to specific contraction types. J Physiol 582:1303–1316PubMedCrossRef Heinemeier KM, Olesen JL, Haddad F, Langberg H, Kjaer M, Baldwin KM, Schjerling P (2007) Expression of collagen and related growth factors in rat tendon and skeletal muscle in response to specific contraction types. J Physiol 582:1303–1316PubMedCrossRef
go back to reference Heissig B, Nishida C, Tashiro Y, Sato Y, Ishihara M, Ohki M, Gritli I, Rosenkvist J, Hattori K (2010) Role of neutrophil-derived matrix metalloproteinase-9 in tissue regeneration. Histol Histopathol 25:765–770PubMed Heissig B, Nishida C, Tashiro Y, Sato Y, Ishihara M, Ohki M, Gritli I, Rosenkvist J, Hattori K (2010) Role of neutrophil-derived matrix metalloproteinase-9 in tissue regeneration. Histol Histopathol 25:765–770PubMed
go back to reference Hellsten Y, Rufener N, Nielsen JJ, Hoier B, Krustrup P, Bangsbo J (2008) Passive leg movement enhances interstitial VEGF protein, endothelial cell proliferation, and eNOS mRNA content in human skeletal muscle. Am J Physiol Regul Integr Comp Physiol 294:R975–R982PubMedCrossRef Hellsten Y, Rufener N, Nielsen JJ, Hoier B, Krustrup P, Bangsbo J (2008) Passive leg movement enhances interstitial VEGF protein, endothelial cell proliferation, and eNOS mRNA content in human skeletal muscle. Am J Physiol Regul Integr Comp Physiol 294:R975–R982PubMedCrossRef
go back to reference Hoier B, Rufener N, Bojsen-Moller J, Bangsbo J, Hellsten Y (2010) The effect of passive movement training on angiogenic factors and capillary growth in human skeletal muscle. J Physiol 588:3833–3845PubMedCrossRef Hoier B, Rufener N, Bojsen-Moller J, Bangsbo J, Hellsten Y (2010) The effect of passive movement training on angiogenic factors and capillary growth in human skeletal muscle. J Physiol 588:3833–3845PubMedCrossRef
go back to reference Janowska-Wieczorek A, Marquez LA, Nabholtz JM, Cabuhat ML, Montaño J, Chang H, Rozmus J, Russell JA, Edwards DR, Turner AR (1999) Growth factors and cytokines upregulate gelatinase expression in bone marrow CD34(+) cells and their transmigration through reconstituted basement membrane. Blood 93:3379–3390PubMed Janowska-Wieczorek A, Marquez LA, Nabholtz JM, Cabuhat ML, Montaño J, Chang H, Rozmus J, Russell JA, Edwards DR, Turner AR (1999) Growth factors and cytokines upregulate gelatinase expression in bone marrow CD34(+) cells and their transmigration through reconstituted basement membrane. Blood 93:3379–3390PubMed
go back to reference Khandoga A, Kessler JS, Hanschen M, Khandoga AG, Burggraf D, Reichel C, Hamann GF, Enders G, Krombach F (2006) Matrix metalloproteinase-9 promotes neutrophil and T cell recruitment and migration in the postischemic liver. J Leukoc Biol 79:1295–1305PubMedCrossRef Khandoga A, Kessler JS, Hanschen M, Khandoga AG, Burggraf D, Reichel C, Hamann GF, Enders G, Krombach F (2006) Matrix metalloproteinase-9 promotes neutrophil and T cell recruitment and migration in the postischemic liver. J Leukoc Biol 79:1295–1305PubMedCrossRef
go back to reference Koskinen SO, Hoyhtya M, Turpeenniemi-Hujanen T, Martikkala V, Makinen TT, Oksa J, Rintamaki H, Lofberg M, Somer H, Takala TE (2001) Serum concentrations of collagen degrading enzymes and their inhibitors after downhill running. Scand J Med Sci Sports 11:9–15PubMedCrossRef Koskinen SO, Hoyhtya M, Turpeenniemi-Hujanen T, Martikkala V, Makinen TT, Oksa J, Rintamaki H, Lofberg M, Somer H, Takala TE (2001) Serum concentrations of collagen degrading enzymes and their inhibitors after downhill running. Scand J Med Sci Sports 11:9–15PubMedCrossRef
go back to reference Lee S, Jilani SM, Nikolova GV, Carpizo D, Iruela-Arispe ML (2005) Processing of VEGF-A by matrix metalloproteinases regulates bioavailability and vascular patterning in tumors. J Cell Biol 169:681–691PubMedCrossRef Lee S, Jilani SM, Nikolova GV, Carpizo D, Iruela-Arispe ML (2005) Processing of VEGF-A by matrix metalloproteinases regulates bioavailability and vascular patterning in tumors. J Cell Biol 169:681–691PubMedCrossRef
go back to reference Lewis MP, Tippett HL, Sinanan AC, Morgan MJ, Hunt NP (2000) Gelatinase-B (matrix metalloproteinase-9; MMP-9) secretion is involved in the migratory phase of human and murine muscle cell cultures. J Muscle Res Cell Motil 21:223–233PubMedCrossRef Lewis MP, Tippett HL, Sinanan AC, Morgan MJ, Hunt NP (2000) Gelatinase-B (matrix metalloproteinase-9; MMP-9) secretion is involved in the migratory phase of human and murine muscle cell cultures. J Muscle Res Cell Motil 21:223–233PubMedCrossRef
go back to reference Lluri G, Jaworski DM (2005) Regulation of TIMP-2, MT1-MMP, and MMP-2 expression during C2C12 differentiation. Muscle Nerve 32:492–499PubMedCrossRef Lluri G, Jaworski DM (2005) Regulation of TIMP-2, MT1-MMP, and MMP-2 expression during C2C12 differentiation. Muscle Nerve 32:492–499PubMedCrossRef
go back to reference Lyons JG, Birkedal-Hansen B, Moore WG, O’Grady RL, Birkedal-Hansen H (1991) Characteristics of a 95-kDa matrix metalloproteinase produced by mammary carcinoma cells. Biochemistry 30:1449–1456PubMedCrossRef Lyons JG, Birkedal-Hansen B, Moore WG, O’Grady RL, Birkedal-Hansen H (1991) Characteristics of a 95-kDa matrix metalloproteinase produced by mammary carcinoma cells. Biochemistry 30:1449–1456PubMedCrossRef
go back to reference Mackey AL, Donnelly AE, Turpeenniemi-Hujanen T, Roper HP (2004) Skeletal muscle collagen content in humans after high-force eccentric contractions. J Appl Physiol 97:197–203PubMedCrossRef Mackey AL, Donnelly AE, Turpeenniemi-Hujanen T, Roper HP (2004) Skeletal muscle collagen content in humans after high-force eccentric contractions. J Appl Physiol 97:197–203PubMedCrossRef
go back to reference Mackey AL, Heinemeier KM, Koskinen SO, Kjaer M (2008) Dynamic adaptation of tendon and muscle connective tissue to mechanical loading. Connect Tissue Res 49:165–168PubMedCrossRef Mackey AL, Heinemeier KM, Koskinen SO, Kjaer M (2008) Dynamic adaptation of tendon and muscle connective tissue to mechanical loading. Connect Tissue Res 49:165–168PubMedCrossRef
go back to reference Madden MC, Byrnes WC, Lebin JA, Batliner ME, Allen DL (2011) Plasma matrix metalloproteinase-9 response to eccentric exercise of the elbow flexors. Eur J Appl Physiol 111:1795–1805PubMedCrossRef Madden MC, Byrnes WC, Lebin JA, Batliner ME, Allen DL (2011) Plasma matrix metalloproteinase-9 response to eccentric exercise of the elbow flexors. Eur J Appl Physiol 111:1795–1805PubMedCrossRef
go back to reference Mitani H, Katayama N, Araki H, Ohishi K, Kobayashi K, Suzuki H, Nishii K, Masuya M, Yasukawa K, Minami N, Shiku H (2000) Activity of interleukin 6 in the differentiation of monocytes to macrophages and dendritic cells. Br J Haematol 109:288–295PubMedCrossRef Mitani H, Katayama N, Araki H, Ohishi K, Kobayashi K, Suzuki H, Nishii K, Masuya M, Yasukawa K, Minami N, Shiku H (2000) Activity of interleukin 6 in the differentiation of monocytes to macrophages and dendritic cells. Br J Haematol 109:288–295PubMedCrossRef
go back to reference Nguyen J, Knapnougel P, Lesavre P, Bauvois B (2005) Inhibition of matrix metalloproteinase-9 by interferons and TGF-beta1 through distinct signalings accounts for reduced monocyte invasiveness. FEBS Lett 579:5487–5493PubMedCrossRef Nguyen J, Knapnougel P, Lesavre P, Bauvois B (2005) Inhibition of matrix metalloproteinase-9 by interferons and TGF-beta1 through distinct signalings accounts for reduced monocyte invasiveness. FEBS Lett 579:5487–5493PubMedCrossRef
go back to reference Opdenakker G, Van den Steen PE, Dubois B, Nelissen I, Van Coillie E, Masure S, Proost P, Van Damme J (2001) Gelatinase B functions as regulator and effector in leukocyte biology. J Leukoc Biol 69:851–859PubMed Opdenakker G, Van den Steen PE, Dubois B, Nelissen I, Van Coillie E, Masure S, Proost P, Van Damme J (2001) Gelatinase B functions as regulator and effector in leukocyte biology. J Leukoc Biol 69:851–859PubMed
go back to reference Reichel CA, Rehberg M, Bihari P, Moser CM, Linder S, Khandoga A, Krombach F (2008) Gelatinases mediate neutrophil recruitment in vivo: evidence for stimulus specificity and a critical role in collagen IV remodeling. J Leukoc Biol 83:864–874PubMedCrossRef Reichel CA, Rehberg M, Bihari P, Moser CM, Linder S, Khandoga A, Krombach F (2008) Gelatinases mediate neutrophil recruitment in vivo: evidence for stimulus specificity and a critical role in collagen IV remodeling. J Leukoc Biol 83:864–874PubMedCrossRef
go back to reference Roach DM, Fitridge RA, Laws PE, Millard SH, Varelias A, Cowled PA (2002) Up-regulation of MMP-2 and MMP-9 leads to degradation of type IV collagen during skeletal muscle reperfusion injury; protection by the MMP inhibitor, doxycycline. Eur J Vasc Endovasc Surg 23:260–269PubMedCrossRef Roach DM, Fitridge RA, Laws PE, Millard SH, Varelias A, Cowled PA (2002) Up-regulation of MMP-2 and MMP-9 leads to degradation of type IV collagen during skeletal muscle reperfusion injury; protection by the MMP inhibitor, doxycycline. Eur J Vasc Endovasc Surg 23:260–269PubMedCrossRef
go back to reference Rosell A, Cuadrado E, Ortega-Aznar A, Hernández-Guillamon M, Lo EH, Montaner J (2008) MMP-9-positive neutrophil infiltration is associated to blood-brain barrier breakdown and basal lamina type IV collagen degradation during hemorrhagic transformation after human ischemic stroke. Stroke 39:1121–1126PubMedCrossRef Rosell A, Cuadrado E, Ortega-Aznar A, Hernández-Guillamon M, Lo EH, Montaner J (2008) MMP-9-positive neutrophil infiltration is associated to blood-brain barrier breakdown and basal lamina type IV collagen degradation during hemorrhagic transformation after human ischemic stroke. Stroke 39:1121–1126PubMedCrossRef
go back to reference Rossignol P, Cambillau M, Bissery A, Mouradian D, Benetos A, Michel JB, Plouin PF, Chatellier G, Jacob MP (2008) Influence of blood sampling procedure on plasma concentrations of matrix metalloproteinases and their tissue inhibitors. Clin Exp Pharmacol Physiol 35:464–469PubMedCrossRef Rossignol P, Cambillau M, Bissery A, Mouradian D, Benetos A, Michel JB, Plouin PF, Chatellier G, Jacob MP (2008) Influence of blood sampling procedure on plasma concentrations of matrix metalloproteinases and their tissue inhibitors. Clin Exp Pharmacol Physiol 35:464–469PubMedCrossRef
go back to reference Rullman E, Rundqvist H, Wagsater D, Fischer H, Eriksson P, Sundberg CJ, Jansson E, Gustafsson T (2007) A single bout of exercise activates matrix metalloproteinase in human skeletal muscle. J Appl Physiol 102:2346–2351PubMedCrossRef Rullman E, Rundqvist H, Wagsater D, Fischer H, Eriksson P, Sundberg CJ, Jansson E, Gustafsson T (2007) A single bout of exercise activates matrix metalloproteinase in human skeletal muscle. J Appl Physiol 102:2346–2351PubMedCrossRef
go back to reference Rullman E, Norrbom J, Stromberg A, Wagsater D, Rundqvist H, Haas T, Gustafsson T (2009) Endurance exercise activates matrix metalloproteinases in human skeletal muscle. J Appl Physiol 106:804–812PubMedCrossRef Rullman E, Norrbom J, Stromberg A, Wagsater D, Rundqvist H, Haas T, Gustafsson T (2009) Endurance exercise activates matrix metalloproteinases in human skeletal muscle. J Appl Physiol 106:804–812PubMedCrossRef
go back to reference Speidl WS, Toller WG, Kaun C, Weiss TW, Pfaffenberger S, Kastl SP, Furnkranz A, Maurer G, Huber K, Metzler H, Wojta J (2004) Catecholamines potentiate LPS-induced expression of MMP-1 and MMP-9 in human monocytes and in the human monocytic cell line U937: possible implications for peri-operative plaque instability. FASEB J 18:603–605PubMed Speidl WS, Toller WG, Kaun C, Weiss TW, Pfaffenberger S, Kastl SP, Furnkranz A, Maurer G, Huber K, Metzler H, Wojta J (2004) Catecholamines potentiate LPS-induced expression of MMP-1 and MMP-9 in human monocytes and in the human monocytic cell line U937: possible implications for peri-operative plaque instability. FASEB J 18:603–605PubMed
go back to reference Suhr F, Rosenwick C, Vassiliadis A, Bloch W, Brixius K (2010) Regulation of extracellular matrix compounds involved in angiogenic processes in short- and long-track elite runners. Scand J Med Sci Sports 20:441–448PubMedCrossRef Suhr F, Rosenwick C, Vassiliadis A, Bloch W, Brixius K (2010) Regulation of extracellular matrix compounds involved in angiogenic processes in short- and long-track elite runners. Scand J Med Sci Sports 20:441–448PubMedCrossRef
go back to reference Van den Steen PE, Dubois B, Nelissen I, Rudd PM, Dwek RA, Opdenakker G (2002) Biochemistry and molecular biology of gelatinase B or matrix metalloproteinase-9 (MMP-9). Crit Rev Biochem Mol Biol 37:375–536PubMedCrossRef Van den Steen PE, Dubois B, Nelissen I, Rudd PM, Dwek RA, Opdenakker G (2002) Biochemistry and molecular biology of gelatinase B or matrix metalloproteinase-9 (MMP-9). Crit Rev Biochem Mol Biol 37:375–536PubMedCrossRef
go back to reference Zimowska M, Brzoska E, Swierczynska M, Streminska W, Moraczewski J (2008) Distinct patterns of MMP-9 and MMP-2 activity in slow and fast twitch skeletal muscle regeneration in vivo. Int J Dev Biol 52:307–314PubMedCrossRef Zimowska M, Brzoska E, Swierczynska M, Streminska W, Moraczewski J (2008) Distinct patterns of MMP-9 and MMP-2 activity in slow and fast twitch skeletal muscle regeneration in vivo. Int J Dev Biol 52:307–314PubMedCrossRef
Metadata
Title
Circulating MMP-9 during exercise in humans
Authors
E. Rullman
K. Olsson
D. Wågsäter
T. Gustafsson
Publication date
01-05-2013
Publisher
Springer-Verlag
Published in
European Journal of Applied Physiology / Issue 5/2013
Print ISSN: 1439-6319
Electronic ISSN: 1439-6327
DOI
https://doi.org/10.1007/s00421-012-2545-z

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