title: Neutrophils are required for 3-methylcholanthrene-initiated, butylated hydroxytoluene-promoted lung carcinogenesis.
abstract: Multiple studies have shown a link between chronic inflammation and lung tumorigenesis. Inbred mouse strains vary in their susceptibility to methylcholanthrene (MCA)-initiated butylated hydroxytoluene (BHT)-promoted lung carcinogenesis. In the present study we investigated whether neutrophils play a role in strain dependent differences in susceptibility to lung tumor promotion. We observed a significant elevation in homeostatic levels of neutrophils in the lungs of tumor-susceptible BALB/cByJ (BALB) mice compared to tumor-resistant C57BL/6J (B6) mice. Additionally, BHT treatment further elevated neutrophil numbers as well as neutrophil chemoattractant keratinocyte-derived cytokine (KC)/chemokine (C-X-C motif) ligand 1 (Cxcl1) levels in BALB lung airways. Lung CD11c+ cells were a major source of KC expression and depletion of neutrophils in BALB mice resulted in a 71% decrease in tumor multiplicity. However, tumor multiplicity did not depend on the presence of T cells, despite the accumulation of T cells following BHT treatment. These data demonstrate that neutrophils are essential to promote tumor growth in the MCA/BHT two-step lung carcinogenesis model.
authors: Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors: Haris G
authors: HG
authors: Vikis
authors: Andrew E
authors: AE
authors: Gelman
authors: Andrew
authors: A
authors: Franklin
authors: Lauren
authors: L
authors: Stein
authors: Amy
authors: A
authors: Rymaszewski
authors: Jihong
authors: J
authors: Zhu
authors: Pengyuan
authors: P
authors: Liu
authors: Jay W
authors: JW
authors: Tichelaar
authors: Alexander S
authors: AS
authors: Krupnick
authors: Ming
authors: M
authors: You
mesh_terms: D000818:Animals; D002084:Butylated Hydroxytoluene / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D002471:Cell Transformation, Neoplastic; D005260:Female; D005434:Flow Cytometry; D007156:Immunologic Memory; D016130:Immunophenotyping; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000276:immunology*; D008748:Methylcholanthrene / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D002273:Carcinogens; D002084:Butylated Hydroxytoluene; D008748:Methylcholanthrene