AMD3100 ameliorates cigarette smoke-induced emphysema-like manifestations in mice
| Autor: | Matthew J. Justice, Keith L. March, Jacob Saliba, Christophe Poirier, Kelly S. Schweitzer, Irina Petrache, Marjorie Albrecht, Houssam Oueini, Daria Barwinska, Hal E. Broxmeyer, Natalia V. Bogatcheva |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine Pathology medicine.medical_specialty Benzylamines Receptors CXCR4 Physiology Cyclams 03 medical and health sciences Mice Bone Marrow Heterocyclic Compounds Physiology (medical) medicine Cigarette smoke Animals COPD Lung Rapid Report business.industry Smoking Cell Biology Lung Injury respiratory system medicine.disease Hematopoietic Stem Cells Chemokine CXCL12 respiratory tract diseases Pulmonary Alveoli 030104 developmental biology medicine.anatomical_structure Pulmonary Emphysema Hematopoietic progenitor cells Female Bone marrow business |
| Popis: | We have shown that cigarette smoke (CS)-induced pulmonary emphysema-like manifestations are preceded by marked suppression of the number and function of bone marrow hematopoietic progenitor cells (HPCs). To investigate whether a limited availability of HPCs may contribute to CS-induced lung injury, we used a Food and Drug Administration-approved antagonist of the interactions of stromal cell-derived factor 1 (SDF-1) with its chemokine receptor CXCR4 to promote intermittent HPC mobilization and tested its ability to limit emphysema-like injury following chronic CS. We administered AMD3100 (5mg/kg) to mice during a chronic CS exposure protocol of up to 24 wk. AMD3100 treatment did not affect either lung SDF-1 levels, which were reduced by CS, or lung inflammatory cell counts. However, AMD3100 markedly improved CS-induced bone marrow HPC suppression and significantly ameliorated emphysema-like end points, such as alveolar airspace size, lung volumes, and lung static compliance. These results suggest that antagonism of SDF-1 binding to CXCR4 is associated with protection of both bone marrow and lungs during chronic CS exposure, thus encouraging future studies of potential therapeutic benefit of AMD3100 in emphysema. |
| Databáze: | OpenAIRE |
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