Biochemical and functional characterization of glycosaminoglycans released from degranulating rat peritoneal mast cells: insights into the physiological role of endogenous heparin

Rebecca Lever; Amir Smailbegovic; Yanira Riffo-Vasquez; Elaine Gray; John Hogwood; Stephen M. Francis; Neville V. Richardson; Clive P. Page; Barbara Mulloy

doi:10.1016/j.pupt.2016.11.002

Biochemical and functional characterization of glycosaminoglycans released from degranulating rat peritoneal mast cells: insights into the physiological role of endogenous heparin

Rebecca Lever, Amir Smailbegovic, Yanira Riffo-Vasquez, Elaine Gray, John Hogwood, Stephen M. Francis, Neville V. Richardson, Clive P. Page, Barbara Mulloy

Research output: Contribution to journal › Article › peer-review

Abstract

The properties of commercially prepared heparin as an anticoagulant and antithrombotic agent in medicine are better understood than is the physiological role of heparin in its native form, where it is uniquely found in the secretory granules of mast cells. In the present study we have isolated and characterised the glycosaminoglycans (GAGs) released from degranulating rat peritoneal mast cells. Analysis of the GAGs by NMR spectroscopy showed the presence of both heparin and the galactosaminoglycan dermatan sulphate; heparinase digestion profiles and measurements of anticoagulant activity were consistent with this finding. The rat peritoneal mast cell GAGs significantly inhibited accumulation of leukocytes in the rat peritoneal cavity in response to IL-1β (p < 0.05, n = 6/group), and inhibited adhesion and diapedesis of leukocytes in the inflamed rat cremasteric microcirculation in response to LPS (p < 0.001, n = 4/group). FTIR spectra of human umbilical vein endothelial cells (HUVECs) were altered by treatment of the cells with heparin degrading enzymes, and restored by the addition of exogenous heparin. In conclusion, we have shown that rat peritoneal mast cells contain a mixture of GAGs that possess anticoagulant and anti-inflammatory properties.

Original language	English
Pages (from-to)	96-102
Number of pages	7
Journal	Pulmonary Pharmacology & Therapeutics
Volume	41
Early online date	3 Nov 2016
DOIs	https://doi.org/10.1016/j.pupt.2016.11.002
Publication status	Published - Dec 2016

Keywords

Heparin
Mast cells
Dermatan sulphate
Glycosaminoglycan

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.pupt.2016.11.002

Francis_2016_PPT_Glycosaminoglycans_AAM
© 2016 Published by Elsevier Ltd. This work has been made available online in accordance with the publisher’s policies. This is the author created, accepted version manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at: https://doi.org/10.1016/j.pupt.2016.11.002
Accepted author manuscript, 1.58 MB

ENDOGENOUS HEPARIN FROM MAST CELLS: Endogenous heparin from mast cells: a role in regulating inflammation cell recruitment
Richardson, N. V. (PI)
The Wellcome Trust
1/08/03 → 31/07/05
Project: Standard

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Lever, R., Smailbegovic, A., Riffo-Vasquez, Y., Gray, E., Hogwood, J., Francis, S. M., Richardson, N. V., Page, C. P., & Mulloy, B. (2016). Biochemical and functional characterization of glycosaminoglycans released from degranulating rat peritoneal mast cells: insights into the physiological role of endogenous heparin. Pulmonary Pharmacology & Therapeutics, 41, 96-102. https://doi.org/10.1016/j.pupt.2016.11.002

@article{57c043e3214c4f9ca855f7bdb352f968,

title = "Biochemical and functional characterization of glycosaminoglycans released from degranulating rat peritoneal mast cells: insights into the physiological role of endogenous heparin",

abstract = "The properties of commercially prepared heparin as an anticoagulant and antithrombotic agent in medicine are better understood than is the physiological role of heparin in its native form, where it is uniquely found in the secretory granules of mast cells. In the present study we have isolated and characterised the glycosaminoglycans (GAGs) released from degranulating rat peritoneal mast cells. Analysis of the GAGs by NMR spectroscopy showed the presence of both heparin and the galactosaminoglycan dermatan sulphate; heparinase digestion profiles and measurements of anticoagulant activity were consistent with this finding. The rat peritoneal mast cell GAGs significantly inhibited accumulation of leukocytes in the rat peritoneal cavity in response to IL-1β (p < 0.05, n = 6/group), and inhibited adhesion and diapedesis of leukocytes in the inflamed rat cremasteric microcirculation in response to LPS (p < 0.001, n = 4/group). FTIR spectra of human umbilical vein endothelial cells (HUVECs) were altered by treatment of the cells with heparin degrading enzymes, and restored by the addition of exogenous heparin. In conclusion, we have shown that rat peritoneal mast cells contain a mixture of GAGs that possess anticoagulant and anti-inflammatory properties.",

keywords = "Heparin, Mast cells, Dermatan sulphate, Glycosaminoglycan",

author = "Rebecca Lever and Amir Smailbegovic and Yanira Riffo-Vasquez and Elaine Gray and John Hogwood and Francis, {Stephen M.} and Richardson, {Neville V.} and Page, {Clive P.} and Barbara Mulloy",

note = "We acknowledge the support of the Wellcome Trust for a grant to RL, CPP and NVR to support some of this work.",

year = "2016",

month = dec,

doi = "10.1016/j.pupt.2016.11.002",

language = "English",

volume = "41",

pages = "96--102",

journal = "Pulmonary Pharmacology & Therapeutics",

issn = "1094-5539",

publisher = "Academic Press/Elsevier ",

}

Lever, R, Smailbegovic, A, Riffo-Vasquez, Y, Gray, E, Hogwood, J, Francis, SM, Richardson, NV, Page, CP & Mulloy, B 2016, 'Biochemical and functional characterization of glycosaminoglycans released from degranulating rat peritoneal mast cells: insights into the physiological role of endogenous heparin', Pulmonary Pharmacology & Therapeutics, vol. 41, pp. 96-102. https://doi.org/10.1016/j.pupt.2016.11.002

Biochemical and functional characterization of glycosaminoglycans released from degranulating rat peritoneal mast cells: insights into the physiological role of endogenous heparin. / Lever, Rebecca; Smailbegovic, Amir; Riffo-Vasquez, Yanira et al.
In: Pulmonary Pharmacology & Therapeutics, Vol. 41, 12.2016, p. 96-102.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Biochemical and functional characterization of glycosaminoglycans released from degranulating rat peritoneal mast cells: insights into the physiological role of endogenous heparin

AU - Lever, Rebecca

AU - Smailbegovic, Amir

AU - Riffo-Vasquez, Yanira

AU - Gray, Elaine

AU - Hogwood, John

AU - Francis, Stephen M.

AU - Richardson, Neville V.

AU - Page, Clive P.

AU - Mulloy, Barbara

N1 - We acknowledge the support of the Wellcome Trust for a grant to RL, CPP and NVR to support some of this work.

PY - 2016/12

Y1 - 2016/12

N2 - The properties of commercially prepared heparin as an anticoagulant and antithrombotic agent in medicine are better understood than is the physiological role of heparin in its native form, where it is uniquely found in the secretory granules of mast cells. In the present study we have isolated and characterised the glycosaminoglycans (GAGs) released from degranulating rat peritoneal mast cells. Analysis of the GAGs by NMR spectroscopy showed the presence of both heparin and the galactosaminoglycan dermatan sulphate; heparinase digestion profiles and measurements of anticoagulant activity were consistent with this finding. The rat peritoneal mast cell GAGs significantly inhibited accumulation of leukocytes in the rat peritoneal cavity in response to IL-1β (p < 0.05, n = 6/group), and inhibited adhesion and diapedesis of leukocytes in the inflamed rat cremasteric microcirculation in response to LPS (p < 0.001, n = 4/group). FTIR spectra of human umbilical vein endothelial cells (HUVECs) were altered by treatment of the cells with heparin degrading enzymes, and restored by the addition of exogenous heparin. In conclusion, we have shown that rat peritoneal mast cells contain a mixture of GAGs that possess anticoagulant and anti-inflammatory properties.

AB - The properties of commercially prepared heparin as an anticoagulant and antithrombotic agent in medicine are better understood than is the physiological role of heparin in its native form, where it is uniquely found in the secretory granules of mast cells. In the present study we have isolated and characterised the glycosaminoglycans (GAGs) released from degranulating rat peritoneal mast cells. Analysis of the GAGs by NMR spectroscopy showed the presence of both heparin and the galactosaminoglycan dermatan sulphate; heparinase digestion profiles and measurements of anticoagulant activity were consistent with this finding. The rat peritoneal mast cell GAGs significantly inhibited accumulation of leukocytes in the rat peritoneal cavity in response to IL-1β (p < 0.05, n = 6/group), and inhibited adhesion and diapedesis of leukocytes in the inflamed rat cremasteric microcirculation in response to LPS (p < 0.001, n = 4/group). FTIR spectra of human umbilical vein endothelial cells (HUVECs) were altered by treatment of the cells with heparin degrading enzymes, and restored by the addition of exogenous heparin. In conclusion, we have shown that rat peritoneal mast cells contain a mixture of GAGs that possess anticoagulant and anti-inflammatory properties.

KW - Heparin

KW - Mast cells

KW - Dermatan sulphate

KW - Glycosaminoglycan

U2 - 10.1016/j.pupt.2016.11.002

DO - 10.1016/j.pupt.2016.11.002

M3 - Article

SN - 1094-5539

VL - 41

SP - 96

EP - 102

JO - Pulmonary Pharmacology & Therapeutics

JF - Pulmonary Pharmacology & Therapeutics

ER -

Biochemical and functional characterization of glycosaminoglycans released from degranulating rat peritoneal mast cells: insights into the physiological role of endogenous heparin

Abstract

Keywords

UN SDGs

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ENDOGENOUS HEPARIN FROM MAST CELLS: Endogenous heparin from mast cells: a role in regulating inflammation cell recruitment

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