title: Lung tumor growth is stimulated in IFN-gamma-/- mice and inhibited in IL-4Ralpha-/- mice.
abstract: BACKGROUND
  Alternative (M2) macrophage activation is associated with tumor development in many tumor types, including those in the lung. Herein the biological consequences of forcing classical (M1) or alternative (M2) macrophage activation on lung tumor development are examined.
  
  
  METHODS
  Urethane-induced lung tumor multiplicity and size were compared in IFN-gamma(-/-) mice which lack M1 macrophage activation, IL-4Ralpha(-/-) mice which lack M2 macrophage activation, and wild-type BALB/cJ (background strain of the IFN-gamma(-/-) and IL-4Ralpha(-/-) mice) mice. Tumor-associated macrophage (TAM) and bone marrow-derived monocyte (BDMC) activation were each examined.
  
  
  RESULTS
  The TAMs and BDMCs in the IFN-gamma(-/-) mice exhibited M2 activation, and their lung tumors were significantly larger than those in the wild-type mice. In contrast, urethane-treated IL-4Ralpha(-/-) mice, whose TAMs and BDMCs were M1 activated, developed smaller tumors than the wild-type mice.
  
  
  CONCLUSIONS
  Altered innate immunity can diminish or accelerate lung tumor progression in response to defective cytokine signaling.
authors.affiliation: Department of Pharmaceutical Sciences, University of Colorado at Denver, Aurora, CO 80045, USA.
authors.forename: Elizabeth F
authors.initials: EF
authors.lastname: Redente
authors.forename: Lori D
authors.initials: LD
authors.lastname: Dwyer-Nield
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Barrett
authors.forename: David W H
authors.initials: DW
authors.lastname: Riches
authors.forename: Alvin M
authors.initials: AM
authors.lastname: Malkinson
mesh_terms: D000818:Animals; D005260:Female; D005455:Fluorescent Antibody Technique; D007113:Immunity, Innate; D007124:Immunoenzyme Techniques; D007371:Interferon-gamma / Q000502:physiology*; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D008262:Macrophage Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011956:Receptors, Cell Surface / Q000502:physiology*; D053662:Interleukin-4 Receptor alpha Subunit
chemical_list: D007371:Interferon-gamma; D011956:Receptors, Cell Surface; C504002:Il4ra protein, mouse; D053662:Interleukin-4 Receptor alpha Subunit