Rho-kinase regulates adhesive and mechanical mechanisms of pulmonary recruitment of neutrophils in abdominal sepsis.
Palani, Karzan LU ; Rahman, Milladur LU
; Hasan, Zirak
LU
; Zhang, Su
LU
; Qi, Zhongquan
LU
; Jeppsson, Bengt
LU
and Thorlacius, Henrik
LU
(2012)
In European Journal of Pharmacology
682(1-3).
p.181-187
- Abstract
- We hypothesized that Rho-kinase signaling plays a role in mechanical and adhesive mechanisms of neutrophil accumulation in lung. Male C57BL/6 mice were treated with the Rho-kinase inhibitor Y-27632 prior to cecal ligation and puncture (CLP). Lung levels of myeloperoxidase (MPO) and histological tissue damage were determined 6h and 24h after CLP. Expression of Mac-1 and F-actin formation in neutrophils were quantified by using flow cytometry 6h after CLP. Mac-1 expression and F-actin formation were also determined in isolated neutrophils up to 3h after stimulation with CXCL2. Labeled and activated neutrophils co-incubated with Y-27632, an anti-Mac-1 antibody and cytochalasin B were adoptively transferred to CLP mice. Y-27632 reduced the... (More)
- We hypothesized that Rho-kinase signaling plays a role in mechanical and adhesive mechanisms of neutrophil accumulation in lung. Male C57BL/6 mice were treated with the Rho-kinase inhibitor Y-27632 prior to cecal ligation and puncture (CLP). Lung levels of myeloperoxidase (MPO) and histological tissue damage were determined 6h and 24h after CLP. Expression of Mac-1 and F-actin formation in neutrophils were quantified by using flow cytometry 6h after CLP. Mac-1 expression and F-actin formation were also determined in isolated neutrophils up to 3h after stimulation with CXCL2. Labeled and activated neutrophils co-incubated with Y-27632, an anti-Mac-1 antibody and cytochalasin B were adoptively transferred to CLP mice. Y-27632 reduced the CLP-induced pulmonary injury and MPO activity as well as Mac-1 on neutrophils. Neutrophil F-actin formation peaked at 6h and returned to baseline levels 24h after CLP induction. Rho-kinase inhibition decreased CLP-provoked F-actin formation in neutrophils. CXCL2 rapidly increased Mac-1 expression and F-actin formation in neutrophils. Co-incubation with Y-27632 abolished CXCL2-induced Mac-1 up-regulation and formation of F-actin in neutrophils. Notably, co-incubation with cytochalasin B inhibited formation of F-actin but did not reduce Mac-1 expression on activated neutrophils. Adoptive transfer experiments revealed that co-incubation of neutrophils with the anti-Mac-1 antibody or cytochalasin B significantly decreased pulmonary accumulation of neutrophils in septic mice. Our data show that targeting Rho-kinase effectively reduces neutrophil recruitment and tissue damage in abdominal sepsis. Moreover, these findings demonstrate that Rho-kinase-dependent neutrophil accumulation in septic lung injury is regulated by both adhesive and mechanical mechanisms. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2432439
- author
- Palani, Karzan
LU
; Rahman, Milladur
LU
; Hasan, Zirak
LU
; Zhang, Su
LU
; Qi, Zhongquan
LU
; Jeppsson, Bengt
LU
and Thorlacius, Henrik
LU
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- in
- European Journal of Pharmacology
- volume
- 682
- issue
- 1-3
- pages
- 181 - 187
- publisher
- Elsevier
- external identifiers
-
- wos:000302982400024
- pmid:22374257
- scopus:84862793613
- pmid:22374257
- ISSN
- 1879-0712
- DOI
- 10.1016/j.ejphar.2012.02.022
- language
- English
- LU publication?
- yes
- id
- 01acda08-0032-4650-8945-1aef3f31e148 (old id 2432439)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/22374257?dopt=Abstract
- date added to LUP
- 2016-04-04 08:14:47
- date last changed
- 2022-02-20 21:29:10
@article{01acda08-0032-4650-8945-1aef3f31e148,
abstract = {{We hypothesized that Rho-kinase signaling plays a role in mechanical and adhesive mechanisms of neutrophil accumulation in lung. Male C57BL/6 mice were treated with the Rho-kinase inhibitor Y-27632 prior to cecal ligation and puncture (CLP). Lung levels of myeloperoxidase (MPO) and histological tissue damage were determined 6h and 24h after CLP. Expression of Mac-1 and F-actin formation in neutrophils were quantified by using flow cytometry 6h after CLP. Mac-1 expression and F-actin formation were also determined in isolated neutrophils up to 3h after stimulation with CXCL2. Labeled and activated neutrophils co-incubated with Y-27632, an anti-Mac-1 antibody and cytochalasin B were adoptively transferred to CLP mice. Y-27632 reduced the CLP-induced pulmonary injury and MPO activity as well as Mac-1 on neutrophils. Neutrophil F-actin formation peaked at 6h and returned to baseline levels 24h after CLP induction. Rho-kinase inhibition decreased CLP-provoked F-actin formation in neutrophils. CXCL2 rapidly increased Mac-1 expression and F-actin formation in neutrophils. Co-incubation with Y-27632 abolished CXCL2-induced Mac-1 up-regulation and formation of F-actin in neutrophils. Notably, co-incubation with cytochalasin B inhibited formation of F-actin but did not reduce Mac-1 expression on activated neutrophils. Adoptive transfer experiments revealed that co-incubation of neutrophils with the anti-Mac-1 antibody or cytochalasin B significantly decreased pulmonary accumulation of neutrophils in septic mice. Our data show that targeting Rho-kinase effectively reduces neutrophil recruitment and tissue damage in abdominal sepsis. Moreover, these findings demonstrate that Rho-kinase-dependent neutrophil accumulation in septic lung injury is regulated by both adhesive and mechanical mechanisms.}},
author = {{Palani, Karzan and Rahman, Milladur and Hasan, Zirak and Zhang, Su and Qi, Zhongquan and Jeppsson, Bengt and Thorlacius, Henrik}},
issn = {{1879-0712}},
language = {{eng}},
number = {{1-3}},
pages = {{181--187}},
publisher = {{Elsevier}},
series = {{European Journal of Pharmacology}},
title = {{Rho-kinase regulates adhesive and mechanical mechanisms of pulmonary recruitment of neutrophils in abdominal sepsis.}},
url = {{http://dx.doi.org/10.1016/j.ejphar.2012.02.022}},
doi = {{10.1016/j.ejphar.2012.02.022}},
volume = {{682}},
year = {{2012}},
}