title: Pulmonary expression of leukemia inhibitory factor induces B cell hyperplasia and confers protection in hyperoxia.
abstract: Leukemia inhibitory factor (LIF) is produced by a large number of pulmonary cells in response to diverse stimuli. Exaggerated levels of LIF have also been detected in the adult respiratory distress syndrome and other disorders. The biologic effects of LIF in the lung, however, have not been elucidated. To define the respiratory effects of LIF, we generated transgenic mice in which human LIF was selectively targeted to the mature lung. In these mice, transgene activation caused an impressive increase in bronchoalveolar lavage (BAL) cellularity with a significant increase in BAL and tissue B lymphocytes. LIF also conferred protection in 100% O2 where it decreased alveolar-capillary protein leak and enhanced survival. This protective effect was associated with the induction of interleukin (IL)-6 mRNA and protein. LIF transgenic mice with a null mutation in IL-6 were more sensitive to the toxic effects of 100% O2 than LIF-transgenic animals with a wild-type IL-6 locus. These studies demonstrate that LIF induces B cell hyperplasia and confers protection in hyperoxic acute lung injury. They also demonstrate that LIF induces IL-6 and that the protective effects of LIF are mediated, in part, via this inductive event. LIF may be an important regulator of B cell-mediated responses and oxidant injury in the lung.
authors.affiliation: Section of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520-8057, USA.
authors.forename: Jingming
authors.initials: J
authors.lastname: Wang
authors.forename: Qingsheng
authors.initials: Q
authors.lastname: Chen
authors.forename: Jonathan
authors.initials: J
authors.lastname: Corne
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhu
authors.forename: Chun Geun
authors.initials: CG
authors.lastname: Lee
authors.forename: Vineet
authors.initials: V
authors.lastname: Bhandari
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Homer
authors.forename: Jack A
authors.initials: JA
authors.lastname: Elias
mesh_terms: D000208:Acute Disease; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D015870:Gene Expression / Q000276:immunology; D006131:Growth Inhibitors / Q000235:genetics*; D018496:Hyperoxia / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D053605:Leukemia Inhibitory Factor; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D008222:Lymphokines / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity; D010100:Oxygen / Q000633:toxicity; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D006131:Growth Inhibitors; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D012333:RNA, Messenger; D010100:Oxygen