Aarhus University Seal / Aarhus Universitets segl

Jens Randel Nyengaard

GM-CSF mediates alveolar epithelial type II cell changes, but not emphysema-like pathology, in SP-D-deficient mice

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Matthias Ochs, University of Göttingen, University of California, San Francisco
  • ,
  • Lars Knudsen, University of Göttingen
  • ,
  • Lennell Allen, University of California, San Francisco
  • ,
  • Amber Stumbaugh, University of California, San Francisco
  • ,
  • Stacey Leviitt, University of California, San Francisco
  • ,
  • Jens R. Nyengaard
  • Samuel Hawgood, University of California, San Francisco

Surfactant protein D (SP-D) is a member of the collectin subfamily of C-type lectins, pattern recognition proteins participating in the innate immune response. Gene-targeted mice deficient in SP-D develop abnormalities in surfactant homeostasis, hyperplasia of alveolar epithelial type II cells, and emphysema-like pathology. Granulocyte/macrophage colony-stimulating factor (GM-CSF) is required for terminal differentiation and subsequent activation of alveolar macrophages, including the expression of matrix metalloproteinases and reactive oxygen species, factors thought to contribute to lung remodeling. Type II cells also express the GM-CSF receptor. Thus we hypothesized GM-CSF might mediate some or all of the cellular and structural abnormalities in the lungs of SP-D-deficient mice. To test this, SP-D (D-G+) and GM-CSF (D+G-) single knockout mice as well as double knockout mice deficient for both SP-D and GM-CSF (D-G-) were analyzed by design-based stereology. Compared with wild type, D-G+ as well as D+G- mice showed decreased alveolar numbers, increased alveolar sizes, and decreased alveolar epithelial surface areas. These emphysema-like changes were present to a greater extent in D-G-mice. D-G+ mice developed type II cell hyperplasia and hypertrophy with increased intracellular surfactant pools, whereas D+G-mice had smaller type II cells with decreased intracellular surfactant pools. In contrast to the emphysematous changes, the type II cell alterations were mostly corrected in D-G- mice. These results indicate that GM-CSF-dependent macrophage activity is not necessary for emphysema development in SP-D-deficient mice, but that type II cell metabolism and proliferation are, either directly or indirectly, regulated by GM-CSF in this model.

Original languageEnglish
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume287
Issue6
Pages (from-to)L1333-L1341
Number of pages9
ISSN1040-0605
DOIs
Publication statusPublished - 1 Dec 2004

    Research areas

  • Alveolar macrophages, Collectins, Granulocyte/macrophage colony-stimulating factor, Stereology, Surfactant protein D

See relations at Aarhus University Citationformats

ID: 156885456