Dual phenotypic characteristics of P-selectin in a mouse model of hemorrhagic shock and hepatectomy.
Hemorrhagic shock
Inflammation
Liver regeneration
P-selectin
Trauma
Journal
Heliyon
ISSN: 2405-8440
Titre abrégé: Heliyon
Pays: England
ID NLM: 101672560
Informations de publication
Date de publication:
Aug 2023
Aug 2023
Historique:
received:
13
03
2023
revised:
14
07
2023
accepted:
21
07
2023
medline:
9
8
2023
pubmed:
9
8
2023
entrez:
9
8
2023
Statut:
epublish
Résumé
Membrane-bound P-selectin induces endothelial adhesion of leucocytes and amplifies organ inflammations during major trauma, while soluble P-selectin (sP-sel) mediates survival rescue properties. This study characterized the differential effects of P-selectin in a "2-hit" model of hemorrhagic shock (HS) and partial hepatectomy (PH). HS was induced by withdrawing blood (0.3 mL) directly from the mouse femoral arteries. 70% or 50% of liver volumes were resected after inducing HS. Time of survival in P-selectin deficient (Selp -/-) mice treated with and without intraperitoneal injections of recombinant P-sel IgG-Fc fusion proteins (rP-sel-Fc, 1.5 mg/kg) were recorded for up to 72h after injury. In addition, liver regeneration at 72h after HS and 50% PH was assessed in wild-type and Selp -/- mice. Compared to wild-types, Selp -/- mice had significantly higher mortality rates post HS and 70% PH, as none of these animals survived up to 48h postoperatively. The survival curve was restored in Selp -/- mice pre-treated with rP-sel-Fc. In the HS followed by 50% PH experimental arm, liver remnant growth ratios were significantly higher in Selp -/- mice (15.7 ± 3.1 vs 11.7 ± 4.9, P = 0.040). The elevated serum concentrations of alanine aminotransferase post-PH were significantly reduced in Selp -/- mice. Hepatocyte proliferation indices (CYP7a1 and PCNA) expression were enhanced and myeloperoxidase activity in the regenerated remnant liver was reduced in the Selp -/- mice. In critical conditions induced by HS and PH, P-selectin mediates two distinct phenotypic characteristics. Soluble-form circulating P-selectin improves survival in the acute stage of HS and extensive loss of liver parenchyma; membrane-bound P-selectin induces regional pro-inflammatory reactions in the remnant liver after the acute stage of two insults, thereby inhibiting hepatic regeneration. The results of this pre-clinical study may provide molecular mechanistic insight and clinical therapeutic applications of P-selectin in the acute and regenerative phases of traumatic hepatic injury.
Sections du résumé
Background
UNASSIGNED
Membrane-bound P-selectin induces endothelial adhesion of leucocytes and amplifies organ inflammations during major trauma, while soluble P-selectin (sP-sel) mediates survival rescue properties. This study characterized the differential effects of P-selectin in a "2-hit" model of hemorrhagic shock (HS) and partial hepatectomy (PH).
Materials and methods
UNASSIGNED
HS was induced by withdrawing blood (0.3 mL) directly from the mouse femoral arteries. 70% or 50% of liver volumes were resected after inducing HS. Time of survival in P-selectin deficient (Selp -/-) mice treated with and without intraperitoneal injections of recombinant P-sel IgG-Fc fusion proteins (rP-sel-Fc, 1.5 mg/kg) were recorded for up to 72h after injury. In addition, liver regeneration at 72h after HS and 50% PH was assessed in wild-type and Selp -/- mice.
Results
UNASSIGNED
Compared to wild-types, Selp -/- mice had significantly higher mortality rates post HS and 70% PH, as none of these animals survived up to 48h postoperatively. The survival curve was restored in Selp -/- mice pre-treated with rP-sel-Fc. In the HS followed by 50% PH experimental arm, liver remnant growth ratios were significantly higher in Selp -/- mice (15.7 ± 3.1 vs 11.7 ± 4.9, P = 0.040). The elevated serum concentrations of alanine aminotransferase post-PH were significantly reduced in Selp -/- mice. Hepatocyte proliferation indices (CYP7a1 and PCNA) expression were enhanced and myeloperoxidase activity in the regenerated remnant liver was reduced in the Selp -/- mice.
Conclusion
UNASSIGNED
In critical conditions induced by HS and PH, P-selectin mediates two distinct phenotypic characteristics. Soluble-form circulating P-selectin improves survival in the acute stage of HS and extensive loss of liver parenchyma; membrane-bound P-selectin induces regional pro-inflammatory reactions in the remnant liver after the acute stage of two insults, thereby inhibiting hepatic regeneration. The results of this pre-clinical study may provide molecular mechanistic insight and clinical therapeutic applications of P-selectin in the acute and regenerative phases of traumatic hepatic injury.
Identifiants
pubmed: 37554775
doi: 10.1016/j.heliyon.2023.e18627
pii: S2405-8440(23)05835-8
pmc: PMC10404689
doi:
Types de publication
Journal Article
Langues
eng
Pagination
e18627Informations de copyright
© 2023 The Authors. Published by Elsevier Ltd.
Déclaration de conflit d'intérêts
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Références
Chem Res Toxicol. 2009 May;22(5):894-8
pubmed: 19374346
Shock. 1999 Jul;12(1):1-9
pubmed: 10468045
J Hepatol. 2016 Jun;64(6):1403-15
pubmed: 26867490
Ann Transl Med. 2017 May;5(10):206
pubmed: 28603721
Clin Chim Acta. 2015 Feb 2;440:87-92
pubmed: 25444751
World J Surg. 2009 Dec;33(12):2522-37
pubmed: 19760312
Trends Mol Med. 2003 Jun;9(6):263-8
pubmed: 12829015
J Trauma. 2010 Nov;69(5):1011-21
pubmed: 21068605
Int J Surg. 2017 Mar;39:255-259
pubmed: 28193544
Lab Anim. 2015 Apr;49(1 Suppl):81-8
pubmed: 25835741
Cardiovasc Res. 2015 Aug 1;107(3):331-9
pubmed: 25994174
Hepatology. 1999 May;29(5):1494-502
pubmed: 10216134
Sci Rep. 2016 Oct 25;6:35868
pubmed: 27779216
Int Arch Allergy Immunol. 2020;181(11):879-887
pubmed: 32777786
Cells. 2019 Nov 12;8(11):
pubmed: 31718093
Biochemistry (Mosc). 1999 Nov;64(11):1326-35
pubmed: 10611541
J Trauma. 2008 Dec;65(6):1264-9; discussion 1269-70
pubmed: 19077611
J Exp Med. 1999 Mar 15;189(6):931-8
pubmed: 10075976
J Am Coll Surg. 1998 Jul;187(1):22-31
pubmed: 9660021
World J Emerg Surg. 2015 Aug 01;10:34
pubmed: 26236391
World J Surg. 2003 Jun;27(6):703-8
pubmed: 12733001
Virulence. 2017 Oct 3;8(7):1216-1228
pubmed: 28102766
Cytokine. 2015 Dec;76(2):442-448
pubmed: 26375521
J Trauma Acute Care Surg. 2015 Sep;79(3):468-74
pubmed: 26307882
Gene Expr. 2017 Nov 27;17(4):277-287
pubmed: 28893351
Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):11452-7
pubmed: 10500197