Rho-Kinase Signaling Regulates Pulmonary Infiltration of Neutrophils in Abdominal Sepsis via Attenuation of CXC Chemokine Formation and Mac-1 Expression on Neutrophils.
Hasan, Zirak LU ; Palani, Karzan LU ; Rahman, Milladur LU
; Zhang, Su
LU
; Syk, Ingvar
LU
; Jeppsson, Bengt
LU
and Thorlacius, Henrik
LU
(2012)
In Shock
37(3).
p.282-288
- Abstract
- ABSTRACT: Excessive neutrophil infiltration is a major component in septic lung injury, although the signaling mechanisms behind pulmonary recruitment of neutrophils in polymicrobial sepsis remain elusive. Herein, we hypothesized that Rho-kinase activity may play a significant role in pulmonary neutrophil recruitment and tissue damage in abdominal sepsis. Male C57BL/6 mice were treated with the Rho-kinase inhibitor Y-27632 (0.5 or 5 mg/kg) before cecal ligation and puncture. Bronchoalveolar lavage fluid and lung tissue were harvested for analysis of neutrophil infiltration, as well as edema and CXC chemokine formation. Blood was collected for analysis of Mac-1 on neutrophils and CD40L on platelets as well as soluble CD40L and... (More)
- ABSTRACT: Excessive neutrophil infiltration is a major component in septic lung injury, although the signaling mechanisms behind pulmonary recruitment of neutrophils in polymicrobial sepsis remain elusive. Herein, we hypothesized that Rho-kinase activity may play a significant role in pulmonary neutrophil recruitment and tissue damage in abdominal sepsis. Male C57BL/6 mice were treated with the Rho-kinase inhibitor Y-27632 (0.5 or 5 mg/kg) before cecal ligation and puncture. Bronchoalveolar lavage fluid and lung tissue were harvested for analysis of neutrophil infiltration, as well as edema and CXC chemokine formation. Blood was collected for analysis of Mac-1 on neutrophils and CD40L on platelets as well as soluble CD40L and metalloproteinase-9 (MMP-9) in plasma. CLP triggered significant pulmonary damage characterized by neutrophil infiltration, increased levels of CXC chemokines, and edema formation in the lung. Furthermore, CLP up-regulated Mac-1 expression on neutrophils, decreased CD40L on platelets and increased soluble CD40L and MMP-9 in the circulation. Interestingly, inhibition of Rho-kinase dose-dependently decreased CLP-induced neutrophil expression of Mac-1, formation of CXC chemokines and edema as well as neutrophil infiltration and tissue damage in the lung. Moreover, Rho-kinase inhibition significantly reduced sepsis-provoked gene-expression of CXC chemokines in alveolar macrophages. In contrast, Rho-kinase inhibition had no effect on platelet shedding of CD40L or plasma levels of MMP-9 in septic mice. In conclusion, these data demonstrate that the Rho-kinase signaling pathway plays a key role in regulating pulmonary infiltration of neutrophils and tissue injury via regulation of CXC chemokine production in the lung and Mac-1 expression on neutrophils in abdominal sepsis. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2336106
- author
- Hasan, Zirak
LU
; Palani, Karzan
LU
; Rahman, Milladur
LU
; Zhang, Su
LU
; Syk, Ingvar
LU
; Jeppsson, Bengt
LU
and Thorlacius, Henrik
LU
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Shock
- volume
- 37
- issue
- 3
- pages
- 282 - 288
- publisher
- Lippincott Williams & Wilkins
- external identifiers
-
- wos:000300622300009
- pmid:22266975
- scopus:84862776568
- pmid:22266975
- ISSN
- 1540-0514
- DOI
- 10.1097/SHK.0b013e3182426be4
- language
- English
- LU publication?
- yes
- id
- 702980c7-de95-4f49-a280-6fadf0442c7e (old id 2336106)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/22266975?dopt=Abstract
- date added to LUP
- 2016-04-04 08:55:16
- date last changed
- 2022-04-23 18:26:01
@article{702980c7-de95-4f49-a280-6fadf0442c7e,
abstract = {{ABSTRACT: Excessive neutrophil infiltration is a major component in septic lung injury, although the signaling mechanisms behind pulmonary recruitment of neutrophils in polymicrobial sepsis remain elusive. Herein, we hypothesized that Rho-kinase activity may play a significant role in pulmonary neutrophil recruitment and tissue damage in abdominal sepsis. Male C57BL/6 mice were treated with the Rho-kinase inhibitor Y-27632 (0.5 or 5 mg/kg) before cecal ligation and puncture. Bronchoalveolar lavage fluid and lung tissue were harvested for analysis of neutrophil infiltration, as well as edema and CXC chemokine formation. Blood was collected for analysis of Mac-1 on neutrophils and CD40L on platelets as well as soluble CD40L and metalloproteinase-9 (MMP-9) in plasma. CLP triggered significant pulmonary damage characterized by neutrophil infiltration, increased levels of CXC chemokines, and edema formation in the lung. Furthermore, CLP up-regulated Mac-1 expression on neutrophils, decreased CD40L on platelets and increased soluble CD40L and MMP-9 in the circulation. Interestingly, inhibition of Rho-kinase dose-dependently decreased CLP-induced neutrophil expression of Mac-1, formation of CXC chemokines and edema as well as neutrophil infiltration and tissue damage in the lung. Moreover, Rho-kinase inhibition significantly reduced sepsis-provoked gene-expression of CXC chemokines in alveolar macrophages. In contrast, Rho-kinase inhibition had no effect on platelet shedding of CD40L or plasma levels of MMP-9 in septic mice. In conclusion, these data demonstrate that the Rho-kinase signaling pathway plays a key role in regulating pulmonary infiltration of neutrophils and tissue injury via regulation of CXC chemokine production in the lung and Mac-1 expression on neutrophils in abdominal sepsis.}},
author = {{Hasan, Zirak and Palani, Karzan and Rahman, Milladur and Zhang, Su and Syk, Ingvar and Jeppsson, Bengt and Thorlacius, Henrik}},
issn = {{1540-0514}},
language = {{eng}},
number = {{3}},
pages = {{282--288}},
publisher = {{Lippincott Williams & Wilkins}},
series = {{Shock}},
title = {{Rho-Kinase Signaling Regulates Pulmonary Infiltration of Neutrophils in Abdominal Sepsis via Attenuation of CXC Chemokine Formation and Mac-1 Expression on Neutrophils.}},
url = {{http://dx.doi.org/10.1097/SHK.0b013e3182426be4}},
doi = {{10.1097/SHK.0b013e3182426be4}},
volume = {{37}},
year = {{2012}},
}