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Targeting CD162 protects against streptococcal M1 protein-evoked neutrophil recruitment and lung injury

Zhang, Songen LU ; Song, Lei LU ; Wang, Yongzhi LU ; Herwald, Heiko LU and Thorlacius, Henrik LU (2013) In American Journal of Physiology: Lung Cellular and Molecular Physiology 305(10). p.756-763
Abstract
Streptococcus pyogenes of the M1 serotype can cause streptococcal toxic shock syndrome and acute lung damage. CD162 is an adhesion molecule that has been reported to mediate neutrophil recruitment in acute inflammatory reactions. In this study, the purpose was to investigate the role of CD162 in M1 protein-provoked lung injury. Male C57BL/6 mice were treated with monoclonal antibody directed against CD162 or a control antibody before M1 protein challenge. Edema, neutrophil infiltration, and CXC chemokines were determined in the lung, 4 h after M1 protein administration. Fluorescence intravital microscopy was used to analyze leukocyte-endothelium interactions in the pulmonary microcirculation. Inhibition of CD162 reduced M1 protein-provoked... (More)
Streptococcus pyogenes of the M1 serotype can cause streptococcal toxic shock syndrome and acute lung damage. CD162 is an adhesion molecule that has been reported to mediate neutrophil recruitment in acute inflammatory reactions. In this study, the purpose was to investigate the role of CD162 in M1 protein-provoked lung injury. Male C57BL/6 mice were treated with monoclonal antibody directed against CD162 or a control antibody before M1 protein challenge. Edema, neutrophil infiltration, and CXC chemokines were determined in the lung, 4 h after M1 protein administration. Fluorescence intravital microscopy was used to analyze leukocyte-endothelium interactions in the pulmonary microcirculation. Inhibition of CD162 reduced M1 protein-provoked accumulation of neutrophils, edema, and CXC chemokine formation in the lung by >54%. Moreover, immunoneutralization of CD162 abolished leukocyte rolling and firm adhesion in pulmonary venules of M1 protein-treated animals. In addition, inhibition of CD162 decreased M1 protein-induced capillary trapping of leukocytes in the lung microvasculature and improved microvascular perfusion in the lungs of M1 protein-treated animals. Our findings suggest that CD162 plays an important role in M1 protein-induced lung damage by regulating leukocyte rolling in pulmonary venules. Consequently, inhibition of CD162 attenuates M1 protein-evoked leukocyte adhesion and extravasation in the lung. Thus, our results suggest that targeting the CD162 might pave the way for novel opportunities to protect against pulmonary damage in streptococcal infections. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
adhesion, chemokines, inflammation and leukocyte
in
American Journal of Physiology: Lung Cellular and Molecular Physiology
volume
305
issue
10
pages
756 - 763
publisher
American Physiological Society
external identifiers
  • wos:000327397600009
  • scopus:84887582589
ISSN
1522-1504
DOI
10.1152/ajplung.00220.2013
language
English
LU publication?
yes
id
f4b7929f-3234-46b2-8769-f35c1f33f225 (old id 4274240)
date added to LUP
2014-02-10 12:27:12
date last changed
2019-02-20 01:35:18
@article{f4b7929f-3234-46b2-8769-f35c1f33f225,
  abstract     = {Streptococcus pyogenes of the M1 serotype can cause streptococcal toxic shock syndrome and acute lung damage. CD162 is an adhesion molecule that has been reported to mediate neutrophil recruitment in acute inflammatory reactions. In this study, the purpose was to investigate the role of CD162 in M1 protein-provoked lung injury. Male C57BL/6 mice were treated with monoclonal antibody directed against CD162 or a control antibody before M1 protein challenge. Edema, neutrophil infiltration, and CXC chemokines were determined in the lung, 4 h after M1 protein administration. Fluorescence intravital microscopy was used to analyze leukocyte-endothelium interactions in the pulmonary microcirculation. Inhibition of CD162 reduced M1 protein-provoked accumulation of neutrophils, edema, and CXC chemokine formation in the lung by >54%. Moreover, immunoneutralization of CD162 abolished leukocyte rolling and firm adhesion in pulmonary venules of M1 protein-treated animals. In addition, inhibition of CD162 decreased M1 protein-induced capillary trapping of leukocytes in the lung microvasculature and improved microvascular perfusion in the lungs of M1 protein-treated animals. Our findings suggest that CD162 plays an important role in M1 protein-induced lung damage by regulating leukocyte rolling in pulmonary venules. Consequently, inhibition of CD162 attenuates M1 protein-evoked leukocyte adhesion and extravasation in the lung. Thus, our results suggest that targeting the CD162 might pave the way for novel opportunities to protect against pulmonary damage in streptococcal infections.},
  author       = {Zhang, Songen and Song, Lei and Wang, Yongzhi and Herwald, Heiko and Thorlacius, Henrik},
  issn         = {1522-1504},
  keyword      = {adhesion,chemokines,inflammation and leukocyte},
  language     = {eng},
  number       = {10},
  pages        = {756--763},
  publisher    = {American Physiological Society},
  series       = {American Journal of Physiology: Lung Cellular and Molecular Physiology},
  title        = {Targeting CD162 protects against streptococcal M1 protein-evoked neutrophil recruitment and lung injury},
  url          = {http://dx.doi.org/10.1152/ajplung.00220.2013},
  volume       = {305},
  year         = {2013},
}