Microhemorrhage is an early event in the pulmonary fibrotic disease of PECAM-1 deficient FVB/n mice

Marta Lishnevsky*, Lena C. Young, Steven J. Woods, Steven D. Groshong, Randall J. Basaraba, John M. Gilchrist, David M. Higgins, Mercedes Gonzalez-Juarrero, Todd A. Bass, William A. Muller, Alan R. Schenkel

*Corresponding author for this work

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Platelet Endothelial Cell Adhesion Molecule 1 (PECAM-1) deficient mice in the FVB/n strain exhibit fatal chronic pulmonary fibrotic disease. The illness occurs in the absence of a detectable pro-inflammatory event. PECAM-1 is vital to the stability of vascular permeability, leukocyte extravasation, clotting of platelets, and clearance of apoptotic cells. We show here that the spontaneous development of fibrotic disease in PECAM-1 deficient FVB/n mice is characterized by early loss of vascular integrity in pulmonary capillaries, resulting in spontaneous microbleeds. Hemosiderin-positive macrophages were found in interstitial spaces and bronchoalveolar lavage (BAL) fluid in relatively healthy animals. We also observed a gradually increasing presence of hemosiderin-positive macrophages and fibrin deposition in the advanced stages of disease, corresponding to the accumulation of collagen, IL-10 expression, and myofibroblasts expressing alpha smooth muscle actin (SMA). Together with the growing evidence that pulmonary microbleeds and coagulation play an active part in human pulmonary fibrosis, this data further supports our hypothesis that PECAM-1 expression is necessary for vascular barrier function control and regulation of homeostasis specifically, in the pulmonary environment.

Original languageEnglish (US)
Pages (from-to)128-136
Number of pages9
JournalExperimental and Molecular Pathology
Volume97
Issue number1
DOIs
StatePublished - Aug 2014

Keywords

  • Interstitial fibrosis
  • Macrophage biology
  • Pulmonary oedema

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Clinical Biochemistry

Fingerprint Dive into the research topics of 'Microhemorrhage is an early event in the pulmonary fibrotic disease of PECAM-1 deficient FVB/n mice'. Together they form a unique fingerprint.

  • Cite this

    Lishnevsky, M., Young, L. C., Woods, S. J., Groshong, S. D., Basaraba, R. J., Gilchrist, J. M., Higgins, D. M., Gonzalez-Juarrero, M., Bass, T. A., Muller, W. A., & Schenkel, A. R. (2014). Microhemorrhage is an early event in the pulmonary fibrotic disease of PECAM-1 deficient FVB/n mice. Experimental and Molecular Pathology, 97(1), 128-136. https://doi.org/10.1016/j.yexmp.2014.06.008