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Targeting CD44 Expressed on Neutrophils Inhibits Lung Damage in Abdominal Sepsis.

Hasan, Zirak LU ; Palani, Karzan LU ; Rahman, Milladur LU and Thorlacius, Henrik LU (2011) In Shock 35. p.567-572
Abstract
Neutrophil infiltration is an insidious feature in septic lung injury, although the specific adhesive mechanisms regulating pulmonary recruitment of neutrophils in polymicrobial sepsis remain elusive. The aim of this present study was to define the role of CD44 in sepsis-induced neutrophil infiltration and lung damage. Mice were treated with a monoclonal antibody against CD44 before cecal ligation and puncture (CLP) induction. Edema formation, bronchoalveolar accumulation of neutrophils, myeloperoxidase activity, and macrophage inflammatory protein-2 (MIP-2) levels in the lung were determined after CLP. Expression of Mac-1 and CD44 on neutrophils was quantified by using flow cytometry. In separate experiments, fluorescent-labeled... (More)
Neutrophil infiltration is an insidious feature in septic lung injury, although the specific adhesive mechanisms regulating pulmonary recruitment of neutrophils in polymicrobial sepsis remain elusive. The aim of this present study was to define the role of CD44 in sepsis-induced neutrophil infiltration and lung damage. Mice were treated with a monoclonal antibody against CD44 before cecal ligation and puncture (CLP) induction. Edema formation, bronchoalveolar accumulation of neutrophils, myeloperoxidase activity, and macrophage inflammatory protein-2 (MIP-2) levels in the lung were determined after CLP. Expression of Mac-1 and CD44 on neutrophils was quantified by using flow cytometry. In separate experiments, fluorescent-labeled neutrophils co-incubated with an anti-CD44 antibody were adoptively transferred to CLP mice. CLP triggered clear-cut lung damage characterized by edema formation, neutrophil infiltration, and increased levels of MIP-2 in the lung. Notably, immunoneutralization of CD44 reduced CLP-induced pulmonary accumulation of neutrophils. In addition, functional inhibition of CD44 decreased CLP-induced lung damage and edema. However, formation of MIP-2 in the lung and neutrophil expression of Mac-1 were intact in septic mice pretreated with the anti-CD44 antibody. Adoptive transfer experiments revealed that neutrophil rather than lung CD44 mediates neutrophil accumulation in septic lung injury. Moreover, administration of hyaluronidase had no effect on CLP-induced neutrophil recruitment and tissue damage in the lung. Our data demonstrate that CD44 contributes to pulmonary infiltration of neutrophils and lung damage associated with abdominal sepsis. Thus, these novel findings suggest that CD44 may serve as a target to protect against lung injury in polymicrobial sepsis. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Shock
volume
35
pages
567 - 572
publisher
BioMedical Press
external identifiers
  • wos:000290662700005
  • pmid:21330943
  • scopus:79957904183
ISSN
1540-0514
DOI
10.1097/SHK.0b013e3182144935
language
English
LU publication?
yes
id
b3701008-74e7-4ae8-829c-857f64d9fb4b (old id 1831691)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21330943?dopt=Abstract
date added to LUP
2011-03-01 17:16:34
date last changed
2017-08-06 04:44:00
@article{b3701008-74e7-4ae8-829c-857f64d9fb4b,
  abstract     = {Neutrophil infiltration is an insidious feature in septic lung injury, although the specific adhesive mechanisms regulating pulmonary recruitment of neutrophils in polymicrobial sepsis remain elusive. The aim of this present study was to define the role of CD44 in sepsis-induced neutrophil infiltration and lung damage. Mice were treated with a monoclonal antibody against CD44 before cecal ligation and puncture (CLP) induction. Edema formation, bronchoalveolar accumulation of neutrophils, myeloperoxidase activity, and macrophage inflammatory protein-2 (MIP-2) levels in the lung were determined after CLP. Expression of Mac-1 and CD44 on neutrophils was quantified by using flow cytometry. In separate experiments, fluorescent-labeled neutrophils co-incubated with an anti-CD44 antibody were adoptively transferred to CLP mice. CLP triggered clear-cut lung damage characterized by edema formation, neutrophil infiltration, and increased levels of MIP-2 in the lung. Notably, immunoneutralization of CD44 reduced CLP-induced pulmonary accumulation of neutrophils. In addition, functional inhibition of CD44 decreased CLP-induced lung damage and edema. However, formation of MIP-2 in the lung and neutrophil expression of Mac-1 were intact in septic mice pretreated with the anti-CD44 antibody. Adoptive transfer experiments revealed that neutrophil rather than lung CD44 mediates neutrophil accumulation in septic lung injury. Moreover, administration of hyaluronidase had no effect on CLP-induced neutrophil recruitment and tissue damage in the lung. Our data demonstrate that CD44 contributes to pulmonary infiltration of neutrophils and lung damage associated with abdominal sepsis. Thus, these novel findings suggest that CD44 may serve as a target to protect against lung injury in polymicrobial sepsis.},
  author       = {Hasan, Zirak and Palani, Karzan and Rahman, Milladur and Thorlacius, Henrik},
  issn         = {1540-0514},
  language     = {eng},
  pages        = {567--572},
  publisher    = {BioMedical Press},
  series       = {Shock},
  title        = {Targeting CD44 Expressed on Neutrophils Inhibits Lung Damage in Abdominal Sepsis.},
  url          = {http://dx.doi.org/10.1097/SHK.0b013e3182144935},
  volume       = {35},
  year         = {2011},
}