A mouse GM-CSF receptor antibody attenuates neutrophilia in mice exposed to cigarette smoke
| Autor: | Matthew A. Sleeman, A J Coyle, I K Anderson, Roland Kolbeck, Fernando M. Botelho, Martin R. Stämpfli, E S Cohen, N H E Davis, A A Humbles, James K. Nikota, Carla M. T. Bauer |
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| Rok vydání: | 2011 |
| Předmět: |
Antigens
Differentiation T-Lymphocyte Pulmonary and Respiratory Medicine medicine.medical_specialty Neutrophils Genes MHC Class II CD11c Inflammation CD8-Positive T-Lymphocytes Antibodies Mice Antigen Antigens CD Internal medicine medicine Animals Lectins C-Type Receptor Lung Mice Knockout Mice Inbred BALB C medicine.diagnostic_test biology Interleukin-12 Subunit p40 business.industry Smoking Granulocyte-Macrophage Colony-Stimulating Factor Receptors Interleukin-1 Dendritic Cells Neutrophilia CD11c Antigen Bronchoalveolar lavage Endocrinology Receptors Granulocyte-Macrophage Colony-Stimulating Factor biology.protein Female Receptors Chemokine Antibody medicine.symptom business Bronchoalveolar Lavage Fluid CD8 |
| Zdroj: | European Respiratory Journal. 38:285-294 |
| ISSN: | 1399-3003 0903-1936 |
| Popis: | We investigated the role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in a subchronic exposure model of cigarette smoke (CS)-induced inflammation using antibodies directed against GM-CSF or the GM-CSF receptor (GM-CSFR) α-chain. CS-induced mononuclear and neutrophilic inflammation following 4 days of CS exposure in BALB/c mice was assessed in bronchoalveolar lavage (BAL) fluid. An increase in mature dendritic cells (DCs) (CD11c+ and major histocompatibility complex II+) and Gr-1-high neutrophils was also observed by flow cytometric analysis of whole-lung tissue. Daily i.p. injection of 400 μg GM-CSF or GM-CSFR antibody prior to daily smoke exposure attenuated the accumulation of neutrophils within the BAL by 60%. A reduction in mature DCs was also observed. Anti-GM-CSFR antibody administration did not have an effect on the percentage of lung T-cells; however, a significant decrease in activated CD69+ CD8+ T-cells was observed. Anti-GM-CSFR antibody administration decreased the mRNA and protein expression of interleukin-12 p40 and matrix metalloproteinase 12. Taken together, intervention with this receptor antibody implicates the GM-CSF pathway as an important mediator of smoke-induced inflammation. |
| Databáze: | OpenAIRE |
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