Abstract
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.
- Antibody neutralisation
- cigarette smoke
- granulocyte-macrophage colony-stimulating factor
- inflammation
- neutrophils
Footnotes
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Support Statement
J.K. Nikota was supported by Ontario’s Early Research Award program (ERA). M.R. Stämpfli holds a Canadian Institutes for Health Research New Investigator award.
Statement of Interest
Statements of interest for N.H.E. Davis, E.S. Cohen, I.K. Anderson, A.J. Coyle, R. Kolbeck, A.A. Humbles, M.R. Stämpfli and M.A. Sleeman can be found at www.erj.ersjournals.com/site/misc/statements.xhtml
- Received May 14, 2010.
- Accepted February 2, 2011.
- ©ERS 2011