title: A mouse GM-CSF receptor antibody attenuates neutrophilia in mice exposed to cigarette smoke.
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.
authors: Department of Pathology and Molecular Medicine, Centre for Gene Therapeutics, McMaster University, Hamilton, ON, Canada.
authors: F M
authors: FM
authors: Botelho
authors: J K
authors: JK
authors: Nikota
authors: C
authors: C
authors: Bauer
authors: N H E
authors: NH
authors: Davis
authors: E S
authors: ES
authors: Cohen
authors: I K
authors: IK
authors: Anderson
authors: A J
authors: AJ
authors: Coyle
authors: R
authors: R
authors: Kolbeck
authors: A A
authors: AA
authors: Humbles
authors: M R
authors: MR
authors: Stämpfli
authors: M A
authors: MA
authors: Sleeman
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D039521:CD11c Antigen / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D005802:Genes, MHC Class II / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis / Q000276:immunology; D037181:Lectins, C-Type / Q000276:immunology; D008168:Lung / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology*; D019707:Receptors, Chemokine / Q000276:immunology; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology*; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000276:immunology; D012907:Smoking / Q000276:immunology*; D000099192:CD69 Antigens
chemical_list: D000906:Antibodies; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D039521:CD11c Antigen; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D053762:Interleukin-12 Subunit p40; D037181:Lectins, C-Type; D019707:Receptors, Chemokine; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D017472:Receptors, Interleukin-1; D000099192:CD69 Antigens; C503133:Gr-1 protein, mouse