Slit2 Prevents Neutrophil Recruitment and Renal Ischemia-Reperfusion Injury : english
(2013) In Journal of the American Society of Nephrology 24(8). p.1274-1287- Abstract
- Neutrophils recruited to the postischemic kidney contribute to the pathogenesis of ischemia-reperfusion injury (IRI), which is the most common cause of renal failure among hospitalized patients. The Slit family of secreted proteins inhibits chemotaxis of leukocytes by preventing activation of Rho-family GTPases, suggesting that members of this family might modulate the recruitment of neutrophils and the resulting IRI. Here, in static and microfluidic shear assays, Slit2 inhibited multiple steps required for the infiltration of neutrophils into tissue. Specifically, Slit2 blocked the capture and firm adhesion of human neutrophils to inflamed vascular endothelial barriers as well as their subsequent transmigration. To examine whether these... (More)
- Neutrophils recruited to the postischemic kidney contribute to the pathogenesis of ischemia-reperfusion injury (IRI), which is the most common cause of renal failure among hospitalized patients. The Slit family of secreted proteins inhibits chemotaxis of leukocytes by preventing activation of Rho-family GTPases, suggesting that members of this family might modulate the recruitment of neutrophils and the resulting IRI. Here, in static and microfluidic shear assays, Slit2 inhibited multiple steps required for the infiltration of neutrophils into tissue. Specifically, Slit2 blocked the capture and firm adhesion of human neutrophils to inflamed vascular endothelial barriers as well as their subsequent transmigration. To examine whether these observations were relevant to renal IRI, we administered Slit2 to mice before bilateral clamping of the renal pedicles. Assessed at 18 hours after reperfusion, Slit2 significantly inhibited renal tubular necrosis, neutrophil and macrophage infiltration, and rise in plasma creatinine. In vitro, Slit2 did not impair the protective functions of neutrophils, including phagocytosis and superoxide production, and did not inhibit neutrophils from killing the extracellular pathogen Staphylococcus aureus. In vivo, administration of Slit2 did not attenuate neutrophil recruitment or bacterial clearance in mice with ascending Escherichia coli urinary tract infections and did not increase the bacterial load in the livers of mice infected with the intracellular pathogen Listeria monocytogenes. Collectively, these results suggest that Slit2 may hold promise as a strategy to combat renal IRI without compromising the protective innate immune response. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4033761
- author
- Chaturvedi, Swasti
; Yuen, Darren A.
; Bajwa, Amandeep
; Huang, Yi-Wei
; Sokollik, Christiane
; Huang, Liping
; Lam, Grace Y.
; Tole, Soumitra
; Liu, Guang-Ying
; Pan, Jerry
; Chan, Lauren
; Sokolskyy, Yaro
; Puthia, Manoj
; Godaly, Gabriela
LU
; John, Rohan
; Wang, Changsen
; Lee, Warren L.
; Brumell, John H.
; Okusa, Mark D.
and Robinson, Lisa A.
(Less) - organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of the American Society of Nephrology
- volume
- 24
- issue
- 8
- pages
- 1274 - 1287
- publisher
- American Society of Nephrology
- external identifiers
-
- wos:000322909400015
- scopus:84879208347
- pmid:23766538
- ISSN
- 1046-6673
- DOI
- 10.1681/ASN.2012090890
- language
- English
- LU publication?
- yes
- id
- 13de1bf5-0a20-4252-97e6-3bb6e3b71013 (old id 4033761)
- date added to LUP
- 2016-04-01 13:16:01
- date last changed
- 2023-09-02 21:20:26
@article{13de1bf5-0a20-4252-97e6-3bb6e3b71013,
abstract = {{Neutrophils recruited to the postischemic kidney contribute to the pathogenesis of ischemia-reperfusion injury (IRI), which is the most common cause of renal failure among hospitalized patients. The Slit family of secreted proteins inhibits chemotaxis of leukocytes by preventing activation of Rho-family GTPases, suggesting that members of this family might modulate the recruitment of neutrophils and the resulting IRI. Here, in static and microfluidic shear assays, Slit2 inhibited multiple steps required for the infiltration of neutrophils into tissue. Specifically, Slit2 blocked the capture and firm adhesion of human neutrophils to inflamed vascular endothelial barriers as well as their subsequent transmigration. To examine whether these observations were relevant to renal IRI, we administered Slit2 to mice before bilateral clamping of the renal pedicles. Assessed at 18 hours after reperfusion, Slit2 significantly inhibited renal tubular necrosis, neutrophil and macrophage infiltration, and rise in plasma creatinine. In vitro, Slit2 did not impair the protective functions of neutrophils, including phagocytosis and superoxide production, and did not inhibit neutrophils from killing the extracellular pathogen Staphylococcus aureus. In vivo, administration of Slit2 did not attenuate neutrophil recruitment or bacterial clearance in mice with ascending Escherichia coli urinary tract infections and did not increase the bacterial load in the livers of mice infected with the intracellular pathogen Listeria monocytogenes. Collectively, these results suggest that Slit2 may hold promise as a strategy to combat renal IRI without compromising the protective innate immune response.}},
author = {{Chaturvedi, Swasti and Yuen, Darren A. and Bajwa, Amandeep and Huang, Yi-Wei and Sokollik, Christiane and Huang, Liping and Lam, Grace Y. and Tole, Soumitra and Liu, Guang-Ying and Pan, Jerry and Chan, Lauren and Sokolskyy, Yaro and Puthia, Manoj and Godaly, Gabriela and John, Rohan and Wang, Changsen and Lee, Warren L. and Brumell, John H. and Okusa, Mark D. and Robinson, Lisa A.}},
issn = {{1046-6673}},
language = {{eng}},
number = {{8}},
pages = {{1274--1287}},
publisher = {{American Society of Nephrology}},
series = {{Journal of the American Society of Nephrology}},
title = {{Slit2 Prevents Neutrophil Recruitment and Renal Ischemia-Reperfusion Injury : english}},
url = {{http://dx.doi.org/10.1681/ASN.2012090890}},
doi = {{10.1681/ASN.2012090890}},
volume = {{24}},
year = {{2013}},
}