Therapeutic Potential of B-1a Cells in Intestinal Ischemia-Reperfusion Injury.
B-1a cells
Gut
Inflammation
Lung
Neutrophils
TLR4
Journal
The Journal of surgical research
ISSN: 1095-8673
Titre abrégé: J Surg Res
Pays: United States
ID NLM: 0376340
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
received:
22
02
2021
revised:
14
06
2021
accepted:
29
06
2021
pubmed:
17
8
2021
medline:
7
4
2022
entrez:
16
8
2021
Statut:
ppublish
Résumé
Acute mesenteric ischemia is a common surgical emergency. Restoration of blood flow is a critical objective of treating this pathology. However, many patients suffer from ischemia-reperfusion (I/R) injuries at the time of revascularization, requiring prolonged hospitalizations. B-1a cells are a subtype of B lymphocytes with roles in regulating inflammation and tissue injury by spontaneous release of natural IgM and IL-10. We hypothesized that treatment with B-1a cells protects mice from intestinal I/R. Mesenteric ischemia was induced in mice by placing a vascular clip on the superior mesenteric artery for 60 minutes. At the time of reperfusion, B-1a cells or PBS control were instilled into the peritoneal cavity (PerC) of mice. PerC lavage, blood, intestine, and lungs were collected 4 h after reperfusion. Serum organ injury and inflammatory markers such as ALT, AST, LDH, lactate, IL-6, as well as lung and gut histology and myeloperoxidase (MPO) were assessed. In intestinal I/R, B-1a cell frequency and number in the PerC were significantly decreased compared to sham-operated mice. There was an increase in the serum levels of ALT, AST, LDH, lactate, and IL-6 when comparing the vehicle group with the sham group. These increases were significantly reduced in the B-1a cell treated group. B-1a cell treatment significantly decreased the intestine and lung injury scores as well as MPO content, compared to vehicle treated mice. B-1a cell treatment resulted in a reduction of apoptotic cells in these tissues. Serum IgM levels were decreased in intestinal I/R, while treatment with B-1a cells significantly increased their levels towards normal levels. B-1a cell treatment at the time of mesenteric reperfusion ameliorates end organ damage and reduces systemic inflammation through the improvement of serum IgM levels. Preserving B-1a cells pool could serve as a novel therapeutic avenue in intestinal I/R injury.
Sections du résumé
BACKGROUND
Acute mesenteric ischemia is a common surgical emergency. Restoration of blood flow is a critical objective of treating this pathology. However, many patients suffer from ischemia-reperfusion (I/R) injuries at the time of revascularization, requiring prolonged hospitalizations. B-1a cells are a subtype of B lymphocytes with roles in regulating inflammation and tissue injury by spontaneous release of natural IgM and IL-10. We hypothesized that treatment with B-1a cells protects mice from intestinal I/R.
METHODS
Mesenteric ischemia was induced in mice by placing a vascular clip on the superior mesenteric artery for 60 minutes. At the time of reperfusion, B-1a cells or PBS control were instilled into the peritoneal cavity (PerC) of mice. PerC lavage, blood, intestine, and lungs were collected 4 h after reperfusion. Serum organ injury and inflammatory markers such as ALT, AST, LDH, lactate, IL-6, as well as lung and gut histology and myeloperoxidase (MPO) were assessed.
RESULTS
In intestinal I/R, B-1a cell frequency and number in the PerC were significantly decreased compared to sham-operated mice. There was an increase in the serum levels of ALT, AST, LDH, lactate, and IL-6 when comparing the vehicle group with the sham group. These increases were significantly reduced in the B-1a cell treated group. B-1a cell treatment significantly decreased the intestine and lung injury scores as well as MPO content, compared to vehicle treated mice. B-1a cell treatment resulted in a reduction of apoptotic cells in these tissues. Serum IgM levels were decreased in intestinal I/R, while treatment with B-1a cells significantly increased their levels towards normal levels.
CONCLUSIONS
B-1a cell treatment at the time of mesenteric reperfusion ameliorates end organ damage and reduces systemic inflammation through the improvement of serum IgM levels. Preserving B-1a cells pool could serve as a novel therapeutic avenue in intestinal I/R injury.
Identifiants
pubmed: 34399355
pii: S0022-4804(21)00460-1
doi: 10.1016/j.jss.2021.06.070
pmc: PMC8678159
mid: NIHMS1727763
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
326-336Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM129633
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL076179
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM118337
Pays : United States
Informations de copyright
Copyright © 2021. Published by Elsevier Inc.
Références
Nat Rev Immunol. 2010 Nov;10(11):778-86
pubmed: 20948548
Surgery. 2017 Oct;162(4):917-927
pubmed: 28709648
Science. 2012 Feb 3;335(6068):597-601
pubmed: 22245738
Circ Res. 2019 Oct 25;125(10):e55-e70
pubmed: 31549940
Redox Biol. 2015 Dec;6:524-551
pubmed: 26484802
JCI Insight. 2020 Mar 12;5(5):
pubmed: 32027619
Shock. 2001 Jan;15(1):1-10
pubmed: 11198350
Arch Surg. 1999 Dec;134(12):1342-7
pubmed: 10593332
J Exp Med. 1998 Dec 21;188(12):2381-6
pubmed: 9858525
Int Immunol. 2008 Jun;20(6):729-37
pubmed: 18375938
Cell Rep. 2016 Mar 15;14(10):2348-61
pubmed: 26947073
Shock. 2020 Nov;54(5):586-594
pubmed: 32604223
JCI Insight. 2020 Mar 12;5(5):
pubmed: 32027618
J Exp Med. 2014 Jun 2;211(6):1243-56
pubmed: 24821911
Surgery. 2020 Sep;168(3):478-485
pubmed: 32439208
Immunity. 2005 Jul;23(1):7-18
pubmed: 16039575
Am J Respir Cell Mol Biol. 2011 May;44(5):725-38
pubmed: 21531958
Front Immunol. 2020 Sep 11;11:586685
pubmed: 33042165
Crit Care Clin. 2005 Apr;21(2):177-96
pubmed: 15781156
Front Immunol. 2012 Jan 11;2:96
pubmed: 22566885
Am J Pathol. 2011 Feb;178(2):735-43
pubmed: 21281806
J Pathol. 2000 Feb;190(3):255-66
pubmed: 10685060
Immunol Res. 2015 Dec;63(1-3):153-66
pubmed: 26427372
Virulence. 2014 Jan 1;5(1):12-9
pubmed: 24193307
J Leukoc Biol. 2019 Jul;106(1):133-146
pubmed: 30645013
Immunobiology. 2016 Jul;221(7):845-52
pubmed: 26898918
Immunity. 2005 Jul;23(1):1-2
pubmed: 16039572
Acute Med Surg. 2020 Apr 13;7(1):e501
pubmed: 32431842
Nat Rev Immunol. 2016 May 27;16(6):378-91
pubmed: 27231052
Cell Res. 2000 Dec;10(4):245-66
pubmed: 11191348
Methods Mol Biol. 2019;1904:53-81
pubmed: 30539466
J Korean Med Sci. 2012 Jan;27(1):27-35
pubmed: 22219610
J Immunol. 2016 May 15;196(10):4348-57
pubmed: 27183643
Front Immunol. 2012 Apr 04;3:66
pubmed: 22566947
Curr Top Microbiol Immunol. 1996;210:167-79
pubmed: 8565555
Am J Pathol. 2010 May;176(5):2283-91
pubmed: 20348235
J Exp Med. 2011 Jan 17;208(1):67-80
pubmed: 21220451
J Exp Med. 2006 Oct 30;203(11):2541-50
pubmed: 17060475
N Engl J Med. 2011 Feb 17;364(7):656-65
pubmed: 21323543
Nat Rev Immunol. 2010 Dec;10(12):826-37
pubmed: 21088683
Ann N Y Acad Sci. 2013 May;1285:97-114
pubmed: 23692567
Proc Natl Acad Sci U S A. 2004 Mar 16;101(11):3886-91
pubmed: 14999103
J Pediatr Surg. 2005 Mar;40(3):470-7
pubmed: 15793720
J Immunol. 2017 Jul 15;199(2):750-760
pubmed: 28630091
Compr Physiol. 2016 Dec 6;7(1):113-170
pubmed: 28135002
Immunity. 2014 Nov 20;41(5):694-707
pubmed: 25517612
Cell Death Differ. 2017 Apr;24(4):683-693
pubmed: 28157209
Arch Intern Med. 2004 May 24;164(10):1054-62
pubmed: 15159262
Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3320-4
pubmed: 1565622
Curr Opin Immunol. 2008 Apr;20(2):149-57
pubmed: 18434123
Am J Respir Crit Care Med. 2005 Oct 1;172(7):798-806
pubmed: 16020801
Mol Med. 2018 May 29;24(1):26
pubmed: 30134811
Int Rev Cell Mol Biol. 2012;298:229-317
pubmed: 22878108
J Immunol. 2012 Feb 1;188(3):939-45
pubmed: 22262757