TY - JOUR T1 - A Mouse GM-CSFR Antibody Attenuates Neutrophilia in Mice Exposed to Cigarette Smoke JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/09031936.00076210 SP - erj00762-2010 AU - F.M. Botelho AU - J. Nikota AU - C. Bauer AU - N.H.E. Davis AU - E. S. Cohen AU - I.K. Anderson AU - A.J. Coyle AU - R. Kolbeck AU - A.A. Humbles AU - M.R. Stämpfli AU - M.A. Sleeman Y1 - 2011/01/01 UR - http://erj.ersjournals.com/content/early/2011/03/24/09031936.00076210.abstract N2 - We have investigated the role of granulocyte-macrophage-colony stimulating factor (GM-CSF) in a subchronic exposure model of cigarette smoke-induced inflammation using antibodies directed against GM-CSF or the GM-CSF receptor alpha chain.Cigarette smoke induced mononuclear and neutrophilic inflammation following four days of cigarette smoke-exposure in BALB/c mice was assessed in bronchoalveolar lavage fluid (BAL). An increase in mature dendritic cells (CD11c+ and MHC II+) and Gr-1 hi+ neutrophils was also observed by flow cytometric analysis of whole lung tissue.Daily intra-peritoneal injection of 400 μg of a GM-CSF or GM-CSF receptor antibody prior to daily smoke exposure attenuated the accumulation of neutrophils within the BAL by 60%. A reduction in mature dendritic cells was also observed. Anti GM-CSF receptor 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-CSF receptor antibody administration decreased the mRNA and protein expression of IL-12p40 and MMP-12.Taken together, intervention with this receptor antibody implicates the GM-CSF pathway as an important mediator of smoke-induced inflammation. ER -