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Thrombospondin-1 is required for normal murine pulmonary homeostasis and its absence causes pneumonia.

Publication ,  Journal Article
Lawler, J; Sunday, M; Thibert, V; Duquette, M; George, EL; Rayburn, H; Hynes, RO
Published in: J Clin Invest
March 1, 1998

The thrombospondins are a family of extracellular calcium-binding proteins that modulate cellular phenotype. Thrombospondin-1 (TSP-1) reportedly regulates cellular attachment, proliferation, migration, and differentiation in vitro. To explore its function in vivo, we have disrupted the TSP-1 gene by homologous recombination in the mouse genome. Platelets from these mice are completely deficient in TSP-1 protein; however, thrombin-induced platelet aggregation is not diminished. TSP-1-deficient mice display a mild and variable lordotic curvature of the spine that is apparent from birth. These mice also display an increase in the number of circulating white blood cells, with monocytes and eosinophils having the largest percent increases. The brain, heart, kidney, spleen, stomach, intestines, aorta, and liver of TSP-1-deficient mice showed no major abnormalities. However, consistent with high levels of expression of TSP-1 in lung, we observe abnormalities in the lungs of mice that lack the protein. Although normal at birth, histopathological analysis of lungs from 4-wk-old TSP-1-deficient mice reveals extensive acute and organizing pneumonia, with neutrophils and macrophages. The macrophages stain for hemosiderin, indicating that diffuse alveolar hemorrhage is occurring. At later times, the number of neutrophils decreases and a striking increase in the number of hemosiderin-containing macrophages is observed associated with multiple-lineage epithelial hyperplasia and the deposition of collagen and elastin. A thickening and ruffling of the epithelium of the airways results from increasing cell proliferation in TSP-1-deficient mice. These results indicate that TSP-1 is involved in normal lung homeostasis.

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Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

March 1, 1998

Volume

101

Issue

5

Start / End Page

982 / 992

Location

United States

Related Subject Headings

  • Transfection
  • Thrombospondin 1
  • Thrombin
  • Ribonucleases
  • Restriction Mapping
  • Recombination, Genetic
  • Radiography
  • Proteins
  • Pneumonia
  • Platelet Aggregation
 

Citation

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Lawler, J., Sunday, M., Thibert, V., Duquette, M., George, E. L., Rayburn, H., & Hynes, R. O. (1998). Thrombospondin-1 is required for normal murine pulmonary homeostasis and its absence causes pneumonia. J Clin Invest, 101(5), 982–992. https://doi.org/10.1172/JCI1684
Lawler, J., M. Sunday, V. Thibert, M. Duquette, E. L. George, H. Rayburn, and R. O. Hynes. “Thrombospondin-1 is required for normal murine pulmonary homeostasis and its absence causes pneumonia.J Clin Invest 101, no. 5 (March 1, 1998): 982–92. https://doi.org/10.1172/JCI1684.
Lawler J, Sunday M, Thibert V, Duquette M, George EL, Rayburn H, et al. Thrombospondin-1 is required for normal murine pulmonary homeostasis and its absence causes pneumonia. J Clin Invest. 1998 Mar 1;101(5):982–92.
Lawler, J., et al. “Thrombospondin-1 is required for normal murine pulmonary homeostasis and its absence causes pneumonia.J Clin Invest, vol. 101, no. 5, Mar. 1998, pp. 982–92. Pubmed, doi:10.1172/JCI1684.
Lawler J, Sunday M, Thibert V, Duquette M, George EL, Rayburn H, Hynes RO. Thrombospondin-1 is required for normal murine pulmonary homeostasis and its absence causes pneumonia. J Clin Invest. 1998 Mar 1;101(5):982–992.

Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

March 1, 1998

Volume

101

Issue

5

Start / End Page

982 / 992

Location

United States

Related Subject Headings

  • Transfection
  • Thrombospondin 1
  • Thrombin
  • Ribonucleases
  • Restriction Mapping
  • Recombination, Genetic
  • Radiography
  • Proteins
  • Pneumonia
  • Platelet Aggregation