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 journalArticlepeer-review

6 Scopus citations


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
Issue number1
StatePublished - Aug 2014


  • Interstitial fibrosis
  • Macrophage biology
  • Pulmonary oedema

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Pathology and Forensic Medicine


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