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CXCR2/CXCR2 ligand biology during lung transplant ischemia-reperfusion injury
- Source :
- Journal of immunology (Baltimore, Md. : 1950). 175(10)
- Publication Year :
- 2005
-
Abstract
- Lung transplantation is a therapeutic option for a number of end-stage pulmonary disorders. Early lung allograft dysfunction (ischemia-reperfusion injury) continues to be the most common cause of early mortality after lung transplantation and a significant risk factor for the development of bronchiolitis obliterans syndrome. Ischemia-reperfusion injury is characterized histopathologically by lung edema and a neutrophil predominate leukocyte extravasation. The specific mechanism(s) that recruit leukocytes to the lung during post-lung transplantation ischemia-reperfusion injury have not been fully elucidated. Because the ELR+ CXC chemokines are potent neutrophil chemoattractants, we investigated their role during post-lung transplantation ischemic-reperfusion injury. We found elevated levels of multiple ELR+ CXC chemokines in human bronchoalveolar lavage fluid from patients with ischemia-reperfusion injury. Proof of concept studies using a rat orthotopic lung transplantation model of “cold” ischemic-reperfusion injury demonstrated an increase in lung graft neutrophil sequestration and injury. In addition, lung expression of CXCL1, CXCL2/3, and their shared receptor CXCR2 paralleled lung neutrophil infiltration and injury. Importantly, inhibition of CXCR2/CXCR2 ligand interactions in vivo led to a marked reduction in lung neutrophil sequestration and graft injury. Taken together these experiments support the notion that increased expression of ELR+ CXC chemokines and their interaction with CXCR2 plays an important role in the pathogenesis of post-lung transplantation cold ischemia-reperfusion injury.
- Subjects :
- Male
Pathology
medicine.medical_specialty
Neutrophils
medicine.medical_treatment
Immunology
Bronchiolitis obliterans
Lung injury
Ligands
Receptors, Interleukin-8B
Immunology and Allergy
Medicine
Lung transplantation
Animals
Humans
CXC chemokine receptors
Prospective Studies
Lung
medicine.diagnostic_test
Base Sequence
business.industry
DNA
Lung Injury
respiratory system
Middle Aged
medicine.disease
respiratory tract diseases
Rats
Transplantation
Disease Models, Animal
Bronchoalveolar lavage
medicine.anatomical_structure
Case-Control Studies
Reperfusion Injury
Female
business
Reperfusion injury
Chemokines, CXC
Lung Transplantation
Subjects
Details
- ISSN :
- 00221767
- Volume :
- 175
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Accession number :
- edsair.doi.dedup.....78bf5ee79254e014665ab152794b81b6