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Disruption in the Dynamic Balance Between Transforming Growth Factor-β and Granulocyte/Macrophage Colony-Stimulating Factor Signaling Within the Alveolar Space of the Alcoholic Lung: Impact on Epithelial and Macrophage Function

Chapter
Part of the Respiratory Medicine book series (RM, volume 14)

Abstract

The mammalian lung is a remarkably complex and delicate organ that has evolved to serve the principal function of exchanging expired carbon dioxide for inspired oxygen to help fuel aerobic metabolism throughout the body. The fundamental gas exchange structure within the lung is the alveolus and its surrounding capillary network. Intrauterine lung development is exquisitely regulated and progresses through stages, with the formation of alveoli occurring at the end of gestation and in the immediate postnatal period. The signaling molecules that comprise the pluripotential superfamily that includes transforming growth factor-β (TGFβ) are critically involved in the branching morphogenesis and later alveolarization that are vital for normal lung development, but their expression and activity wane rapidly in the postnatal period in the healthy state. In contradistinction, the relative influence of granulocyte/macrophage colony-stimulating factor (GM-CSF) emerges in the immediate prenatal period and throughout normal lung health as the dominant regulator of alveolar functions including the maintenance of the tight epithelial barrier, the formation and recycling of surfactant, and the maturation of the alveolar macrophage, which is the unique resident host immune cell within the lower airways. There is now abundant experimental evidence that chronic alcohol ingestion disrupts the dynamic balance between TGFβ1 and GM-CSF within the lung with profound consequences for alveolar epithelial and macrophage function. In fact, the aberrant expression and activity of TGFβ1 and the consequent dampening of GM-CSF signaling within the lower airways appears to be a fundamental factor that drives the “alcoholic lung phenotype.” This chapter reviews the fundamental roles of these two molecules and their signaling pathways and illustrates the evolving recognition that disruption of their dynamic balance by alcohol renders the lung susceptible to a wide range of pathologies.

Keywords

Transforming growth factor beta (TGFβ) Granulocyte/macrophage colony-stimulating factor (GM-CSF) Alveolar macrophage Alveolar epithelium Phagocytosis Tight junctions 

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Division of Pulmonary, Allergy and Critical Care MedicineEmory University School of Medicine and the Atlanta VA Medical CenterAtlantaUSA
  2. 2.Division of Pulmonary, Allergy and Critical Care MedicineEmory University School of Medicine and the Atlanta VA Medical CenterDecaturUSA

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