Ras regulates alveolar macrophage formation of CXC chemokines and neutrophil activation in streptococcal M1 protein-induced lung injury.
Zhang, Songen LU ; Hwaiz, Rundk LU ; Rahman, Milladur LU
; Herwald, Heiko
LU
and Thorlacius, Henrik
LU
(2014)
In European Journal of Pharmacology
733(Apr 1).
p.45-53
- Abstract
- Streptococcal toxic shock syndrome (STSS) is associated with a high mortality rate. The M1 serotype of Streptococcus pyogenes is most frequently associated with STSS. Herein, we examined the role of Ras signaling in M1 protein-induced lung injury. Male C57BL/6 mice received the Ras inhibitor (farnesylthiosalicylic acid, FTS) prior to M1 protein challenge. Bronchoalveolar fluid and lung tissue were harvested for quantification of neutrophil recruitment, edema and CXC chemokine formation. Neutrophil expression of Mac-1 was quantified by use of flow cytometry. Quantitative RT-PCR was used to determine gene expression of CXC chemokines in alveolar macrophages. Administration of FTS reduced M1 protein-induced neutrophil recruitment, edema... (More)
- Streptococcal toxic shock syndrome (STSS) is associated with a high mortality rate. The M1 serotype of Streptococcus pyogenes is most frequently associated with STSS. Herein, we examined the role of Ras signaling in M1 protein-induced lung injury. Male C57BL/6 mice received the Ras inhibitor (farnesylthiosalicylic acid, FTS) prior to M1 protein challenge. Bronchoalveolar fluid and lung tissue were harvested for quantification of neutrophil recruitment, edema and CXC chemokine formation. Neutrophil expression of Mac-1 was quantified by use of flow cytometry. Quantitative RT-PCR was used to determine gene expression of CXC chemokines in alveolar macrophages. Administration of FTS reduced M1 protein-induced neutrophil recruitment, edema formation and tissue damage in the lung. M1 protein challenge increased Mac-1 expression on neutrophils and CXC chemokine levels in the lung. Inhibition of Ras activity decreased M1 protein-induced expression of Mac-1 on neutrophils and secretion of CXC chemokines in the lung. Moreover, FTS abolished M1 protein-provoked gene expression of CXC chemokines in alveolar macrophages. Ras inhibition decreased chemokine-mediated neutrophil migration in vitro. Taken together, our novel findings indicate that Ras signaling is a potent regulator of CXC chemokine formation and neutrophil infiltration in the lung. Thus, inhibition of Ras activity might be a useful way to antagonize streptococcal M1 protein-triggered acute lung injury. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4430774
- author
- Zhang, Songen
LU
; Hwaiz, Rundk
LU
; Rahman, Milladur
LU
; Herwald, Heiko
LU
and Thorlacius, Henrik
LU
- organization
- publishing date
- 2014
- type
- Contribution to journal
- publication status
- published
- subject
- in
- European Journal of Pharmacology
- volume
- 733
- issue
- Apr 1
- pages
- 45 - 53
- publisher
- Elsevier
- external identifiers
-
- pmid:24704370
- wos:000335918600005
- scopus:84899012482
- pmid:24704370
- ISSN
- 1879-0712
- DOI
- 10.1016/j.ejphar.2014.03.029
- language
- English
- LU publication?
- yes
- id
- 4c248f08-1d28-44b7-8dc2-03b8ea474938 (old id 4430774)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/24704370?dopt=Abstract
- date added to LUP
- 2016-04-01 09:54:51
- date last changed
- 2022-04-27 08:46:40
@article{4c248f08-1d28-44b7-8dc2-03b8ea474938,
abstract = {{Streptococcal toxic shock syndrome (STSS) is associated with a high mortality rate. The M1 serotype of Streptococcus pyogenes is most frequently associated with STSS. Herein, we examined the role of Ras signaling in M1 protein-induced lung injury. Male C57BL/6 mice received the Ras inhibitor (farnesylthiosalicylic acid, FTS) prior to M1 protein challenge. Bronchoalveolar fluid and lung tissue were harvested for quantification of neutrophil recruitment, edema and CXC chemokine formation. Neutrophil expression of Mac-1 was quantified by use of flow cytometry. Quantitative RT-PCR was used to determine gene expression of CXC chemokines in alveolar macrophages. Administration of FTS reduced M1 protein-induced neutrophil recruitment, edema formation and tissue damage in the lung. M1 protein challenge increased Mac-1 expression on neutrophils and CXC chemokine levels in the lung. Inhibition of Ras activity decreased M1 protein-induced expression of Mac-1 on neutrophils and secretion of CXC chemokines in the lung. Moreover, FTS abolished M1 protein-provoked gene expression of CXC chemokines in alveolar macrophages. Ras inhibition decreased chemokine-mediated neutrophil migration in vitro. Taken together, our novel findings indicate that Ras signaling is a potent regulator of CXC chemokine formation and neutrophil infiltration in the lung. Thus, inhibition of Ras activity might be a useful way to antagonize streptococcal M1 protein-triggered acute lung injury.}},
author = {{Zhang, Songen and Hwaiz, Rundk and Rahman, Milladur and Herwald, Heiko and Thorlacius, Henrik}},
issn = {{1879-0712}},
language = {{eng}},
number = {{Apr 1}},
pages = {{45--53}},
publisher = {{Elsevier}},
series = {{European Journal of Pharmacology}},
title = {{Ras regulates alveolar macrophage formation of CXC chemokines and neutrophil activation in streptococcal M1 protein-induced lung injury.}},
url = {{http://dx.doi.org/10.1016/j.ejphar.2014.03.029}},
doi = {{10.1016/j.ejphar.2014.03.029}},
volume = {{733}},
year = {{2014}},
}