The potentiation of myeloperoxidase activity by the glycosaminoglycan- dependent binding of myeloperoxidase to proteins of the extracellular matrix

Lukáš Kubala, Hana Kolářová, Jan Víteček, Silvie Kremserová, Anna Klinke, Denise Lau, Anna L P Chapman, Stephan Baldus, Jason P. Eiserich

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Background Myeloperoxidase (MPO) is an abundant hemoprotein expressed by neutrophil granulocytes that is recognized to play an important role in the development of vascular diseases. Upon degranulation from circulating neutrophil granulocytes, MPO binds to the surface of endothelial cells in an electrostatic-dependent manner and undergoes transcytotic migration to the underlying extracellular matrix (ECM). However, the mechanisms governing the binding of MPO to subendothelial ECM proteins, and whether this binding modulates its enzymatic functions are not well understood. Methods We investigated MPO binding to ECM derived from aortic endothelial cells, aortic smooth muscle cells, and fibroblasts, and to purified ECM proteins, and the modulation of these associations by glycosaminoglycans. The oxidizing and chlorinating potential of MPO upon binding to ECM proteins was tested. Results MPO binds to the ECM proteins collagen IV and fibronectin, and this association is enhanced by the pre-incubation of these proteins with glycosaminoglycans. Correspondingly, an excess of glycosaminoglycans in solution during incubation inhibits the binding of MPO to collagen IV and fibronectin. These observations were confirmed with cell-derived ECM. The oxidizing and chlorinating potential of MPO was preserved upon binding to collagen IV and fibronectin; even the potentiation of MPO activity in the presence of collagen IV and fibronectin was observed. Conclusions Collectively, the data reveal that MPO binds to ECM proteins on the basis of electrostatic interactions, and MPO chlorinating and oxidizing activity is potentiated upon association with these proteins. General significance Our findings provide new insights into the molecular mechanisms underlying the interaction of MPO with ECM proteins.

Original languageEnglish (US)
Pages (from-to)4524-4536
Number of pages13
JournalBiochimica et Biophysica Acta - General Subjects
Volume1830
Issue number10
DOIs
StatePublished - 2013

Fingerprint

Extracellular Matrix Proteins
Glycosaminoglycans
Peroxidase
Fibronectins
Collagen
Extracellular Matrix
Endothelial cells
Static Electricity
Granulocytes
Neutrophils
Endothelial Cells
Fibroblasts
Coulomb interactions
Vascular Diseases
Protein Binding
Smooth Muscle Myocytes
Muscle
Electrostatics
Proteins
Cells

Keywords

  • Cardiovascular disease
  • Collagen IV
  • Endothelium
  • Enzyme activity
  • Fibronectin
  • Inflammation

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

The potentiation of myeloperoxidase activity by the glycosaminoglycan- dependent binding of myeloperoxidase to proteins of the extracellular matrix. / Kubala, Lukáš; Kolářová, Hana; Víteček, Jan; Kremserová, Silvie; Klinke, Anna; Lau, Denise; Chapman, Anna L P; Baldus, Stephan; Eiserich, Jason P.

In: Biochimica et Biophysica Acta - General Subjects, Vol. 1830, No. 10, 2013, p. 4524-4536.

Research output: Contribution to journalArticle

Kubala, L, Kolářová, H, Víteček, J, Kremserová, S, Klinke, A, Lau, D, Chapman, ALP, Baldus, S & Eiserich, JP 2013, 'The potentiation of myeloperoxidase activity by the glycosaminoglycan- dependent binding of myeloperoxidase to proteins of the extracellular matrix', Biochimica et Biophysica Acta - General Subjects, vol. 1830, no. 10, pp. 4524-4536. https://doi.org/10.1016/j.bbagen.2013.05.024
Kubala, Lukáš ; Kolářová, Hana ; Víteček, Jan ; Kremserová, Silvie ; Klinke, Anna ; Lau, Denise ; Chapman, Anna L P ; Baldus, Stephan ; Eiserich, Jason P. / The potentiation of myeloperoxidase activity by the glycosaminoglycan- dependent binding of myeloperoxidase to proteins of the extracellular matrix. In: Biochimica et Biophysica Acta - General Subjects. 2013 ; Vol. 1830, No. 10. pp. 4524-4536.
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abstract = "Background Myeloperoxidase (MPO) is an abundant hemoprotein expressed by neutrophil granulocytes that is recognized to play an important role in the development of vascular diseases. Upon degranulation from circulating neutrophil granulocytes, MPO binds to the surface of endothelial cells in an electrostatic-dependent manner and undergoes transcytotic migration to the underlying extracellular matrix (ECM). However, the mechanisms governing the binding of MPO to subendothelial ECM proteins, and whether this binding modulates its enzymatic functions are not well understood. Methods We investigated MPO binding to ECM derived from aortic endothelial cells, aortic smooth muscle cells, and fibroblasts, and to purified ECM proteins, and the modulation of these associations by glycosaminoglycans. The oxidizing and chlorinating potential of MPO upon binding to ECM proteins was tested. Results MPO binds to the ECM proteins collagen IV and fibronectin, and this association is enhanced by the pre-incubation of these proteins with glycosaminoglycans. Correspondingly, an excess of glycosaminoglycans in solution during incubation inhibits the binding of MPO to collagen IV and fibronectin. These observations were confirmed with cell-derived ECM. The oxidizing and chlorinating potential of MPO was preserved upon binding to collagen IV and fibronectin; even the potentiation of MPO activity in the presence of collagen IV and fibronectin was observed. Conclusions Collectively, the data reveal that MPO binds to ECM proteins on the basis of electrostatic interactions, and MPO chlorinating and oxidizing activity is potentiated upon association with these proteins. General significance Our findings provide new insights into the molecular mechanisms underlying the interaction of MPO with ECM proteins.",
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T1 - The potentiation of myeloperoxidase activity by the glycosaminoglycan- dependent binding of myeloperoxidase to proteins of the extracellular matrix

AU - Kubala, Lukáš

AU - Kolářová, Hana

AU - Víteček, Jan

AU - Kremserová, Silvie

AU - Klinke, Anna

AU - Lau, Denise

AU - Chapman, Anna L P

AU - Baldus, Stephan

AU - Eiserich, Jason P.

PY - 2013

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N2 - Background Myeloperoxidase (MPO) is an abundant hemoprotein expressed by neutrophil granulocytes that is recognized to play an important role in the development of vascular diseases. Upon degranulation from circulating neutrophil granulocytes, MPO binds to the surface of endothelial cells in an electrostatic-dependent manner and undergoes transcytotic migration to the underlying extracellular matrix (ECM). However, the mechanisms governing the binding of MPO to subendothelial ECM proteins, and whether this binding modulates its enzymatic functions are not well understood. Methods We investigated MPO binding to ECM derived from aortic endothelial cells, aortic smooth muscle cells, and fibroblasts, and to purified ECM proteins, and the modulation of these associations by glycosaminoglycans. The oxidizing and chlorinating potential of MPO upon binding to ECM proteins was tested. Results MPO binds to the ECM proteins collagen IV and fibronectin, and this association is enhanced by the pre-incubation of these proteins with glycosaminoglycans. Correspondingly, an excess of glycosaminoglycans in solution during incubation inhibits the binding of MPO to collagen IV and fibronectin. These observations were confirmed with cell-derived ECM. The oxidizing and chlorinating potential of MPO was preserved upon binding to collagen IV and fibronectin; even the potentiation of MPO activity in the presence of collagen IV and fibronectin was observed. Conclusions Collectively, the data reveal that MPO binds to ECM proteins on the basis of electrostatic interactions, and MPO chlorinating and oxidizing activity is potentiated upon association with these proteins. General significance Our findings provide new insights into the molecular mechanisms underlying the interaction of MPO with ECM proteins.

AB - Background Myeloperoxidase (MPO) is an abundant hemoprotein expressed by neutrophil granulocytes that is recognized to play an important role in the development of vascular diseases. Upon degranulation from circulating neutrophil granulocytes, MPO binds to the surface of endothelial cells in an electrostatic-dependent manner and undergoes transcytotic migration to the underlying extracellular matrix (ECM). However, the mechanisms governing the binding of MPO to subendothelial ECM proteins, and whether this binding modulates its enzymatic functions are not well understood. Methods We investigated MPO binding to ECM derived from aortic endothelial cells, aortic smooth muscle cells, and fibroblasts, and to purified ECM proteins, and the modulation of these associations by glycosaminoglycans. The oxidizing and chlorinating potential of MPO upon binding to ECM proteins was tested. Results MPO binds to the ECM proteins collagen IV and fibronectin, and this association is enhanced by the pre-incubation of these proteins with glycosaminoglycans. Correspondingly, an excess of glycosaminoglycans in solution during incubation inhibits the binding of MPO to collagen IV and fibronectin. These observations were confirmed with cell-derived ECM. The oxidizing and chlorinating potential of MPO was preserved upon binding to collagen IV and fibronectin; even the potentiation of MPO activity in the presence of collagen IV and fibronectin was observed. Conclusions Collectively, the data reveal that MPO binds to ECM proteins on the basis of electrostatic interactions, and MPO chlorinating and oxidizing activity is potentiated upon association with these proteins. General significance Our findings provide new insights into the molecular mechanisms underlying the interaction of MPO with ECM proteins.

KW - Cardiovascular disease

KW - Collagen IV

KW - Endothelium

KW - Enzyme activity

KW - Fibronectin

KW - Inflammation

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