Heparin inhibits proinflammatory and promotes anti-inflammatory macrophage polarization under hyperglycemic stress.
Animals
Anti-Inflammatory Agents
/ pharmacology
Anticoagulants
/ pharmacology
Arginase
/ metabolism
Diabetes Mellitus, Experimental
/ physiopathology
Diabetes Mellitus, Type 2
/ physiopathology
Extracellular Matrix
/ metabolism
Female
Glucose
/ metabolism
Heparin
/ pharmacology
Humans
Hyperglycemia
/ immunology
Inflammation
/ etiology
Inflammation Mediators
/ immunology
Interleukin-10
/ metabolism
Macrophages
/ drug effects
Mice
Monocytes
/ drug effects
heparin
hyaluronan
inflammation
macrophage
monocyte
Journal
The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R
Informations de publication
Date de publication:
10 04 2020
10 04 2020
Historique:
received:
20
12
2019
revised:
21
02
2020
pubmed:
29
2
2020
medline:
15
12
2020
entrez:
29
2
2020
Statut:
ppublish
Résumé
Monocytes are rapidly recruited to sites of diabetic complications and differentiate into macrophages. Previously, we showed that rat kidney mesangial cells dividing during hyperglycemic stress abnormally synthesize hyaluronan (HA) in intracellular compartments. This initiates a stress response, resulting in an extracellular HA matrix after division that recruits inflammatory cells. Cell-cell communication among macrophages that are recruited into the glomeruli and the damaged rat mesangial cells leads to diabetic nephropathy, fibrosis, and proteinurea, which are inhibited in heparin-treated diabetic rats. In this study, we found that murine bone marrow-derived macrophages (BMDMs) and a human leukemic cell line, U937 cells, dividing in hyperglycemia also accumulate intracellular HA and that heparin inhibits the HA accumulation. Both cell types expressed increased levels of proinflammatory markers: inducible nitric-oxide synthase and tumor necrosis factor-α, when cultured under hyperglycemic stress, which was inhibited by heparin. Furthermore, the abnormal intracellular HA was also observed in peripheral blood monocytes derived from three different hyperglycemic diabetic mouse models: streptozotocin-treated, high-fat fed, and Ins2Akita. Moreover, peripheral blood monocytes in humans with type 2 diabetes and poorly controlled blood glucose levels (hemoglobin A1c (HbA1c) levels of >7) also had intracellular HA, whereas those with HbA1c of <7, did not. Of note, heparin increased the anti-inflammatory markers arginase 1 and interleukin-10 in murine BMDMs. We conclude that heparin treatment of high glucose-exposed dividing BMDMs promotes an anti-inflammatory tissue-repair phenotype in these cells.
Identifiants
pubmed: 32107314
pii: S0021-9258(17)48581-4
doi: 10.1074/jbc.RA119.012419
pmc: PMC7152777
doi:
Substances chimiques
Anti-Inflammatory Agents
0
Anticoagulants
0
Inflammation Mediators
0
Interleukin-10
130068-27-8
Heparin
9005-49-6
Arginase
EC 3.5.3.1
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
4849-4857Subventions
Organisme : NHLBI NIH HHS
ID : K12 HL141952
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL107147
Pays : United States
Informations de copyright
© 2020 Abbadi et al.
Références
Atherosclerosis. 2004 Jul;175(1):39-49
pubmed: 15186945
Cell Mol Life Sci. 2015 Nov;72(21):4111-26
pubmed: 26210152
Curr Protoc Immunol. 2008 Nov;Chapter 14:Unit 14.1
pubmed: 19016445
Cell Immunol. 2013 Jan;281(1):51-61
pubmed: 23454681
Cardiovasc Res. 2015 Aug 1;107(3):321-30
pubmed: 25990461
Diabetes. 2013 Oct;62(10):3394-403
pubmed: 23835343
Glycobiology. 2000 Mar;10(3):273-81
pubmed: 10704526
Nat Rev Immunol. 2005 Dec;5(12):953-64
pubmed: 16322748
Physiol Rev. 2013 Jan;93(1):137-88
pubmed: 23303908
Nat Rev Immunol. 2011 Oct 25;11(11):750-61
pubmed: 22025054
J Biol Chem. 2014 Apr 18;289(16):11410-20
pubmed: 24569987
J Biomed Biotechnol. 2010;2010:683485
pubmed: 20029630
Biol Chem. 2017 Apr 1;398(4):411-423
pubmed: 27768581
Nat Rev Immunol. 2003 Jan;3(1):23-35
pubmed: 12511873
Physiol Res. 2001;50(6):537-46
pubmed: 11829314
J Clin Invest. 2002 Feb;109(4):525-32
pubmed: 11854325
FEBS J. 2011 May;278(9):1412-8
pubmed: 21362136
Crit Rev Immunol. 2012;32(6):463-88
pubmed: 23428224
Diabetes. 1997 May;46(5):887-94
pubmed: 9133560
Immunity. 2010 May 28;32(5):593-604
pubmed: 20510870
J Biol Chem. 2004 Mar 12;279(11):10279-85
pubmed: 14679194
Free Radic Biol Med. 2013 Jan;54:1-16
pubmed: 23124025
Int J Cancer. 1976 May 15;17(5):565-77
pubmed: 178611
Immunobiology. 2010 Sep-Oct;215(9-10):821-5
pubmed: 20580461
Immunity. 2014 Jul 17;41(1):14-20
pubmed: 25035950
Proc Natl Acad Sci U S A. 2005 Nov 1;102(44):16001-6
pubmed: 16243976
Am J Physiol Renal Physiol. 2006 Jan;290(1):F214-22
pubmed: 16118394
J Immunol. 2000 Jun 15;164(12):6166-73
pubmed: 10843666
Am J Pathol. 2003 Jul;163(1):121-33
pubmed: 12819017
J Clin Invest. 1999 Jan;103(1):27-37
pubmed: 9884331
Transplantation. 2002 Apr 27;73(8):1333-6
pubmed: 11981430
J Immunol. 2009 Aug 1;183(3):1598-606
pubmed: 19592658
J Clin Invest. 2002 Feb;109(4):443-5
pubmed: 11854314
Diabetes. 2005 Sep;54(9):2779-86
pubmed: 16123369
Diabetes. 2012 Nov;61(11):2881-92
pubmed: 22745325
J Biol Chem. 2014 Mar 28;289(13):9418-29
pubmed: 24482224
Crit Rev Immunol. 2001;21(5):399-425
pubmed: 11942557
Front Immunol. 2014 Oct 17;5:514
pubmed: 25368618