title: Microhemorrhage is an early event in the pulmonary fibrotic disease of PECAM-1 deficient FVB/n mice.
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.
authors: Department of Microbiology, Immunology, and Pathology, Colorado State University, 1682 Campus Delivery, Fort Collins, CO 80523, United States. Electronic address: lishnevM@gmail.com.
authors: Marta
authors: M
authors: Lishnevsky
authors: Department of Microbiology, Immunology, and Pathology, Colorado State University, 1682 Campus Delivery, Fort Collins, CO 80523, United States.
authors: Lena C
authors: LC
authors: Young
authors: Department of Microbiology, Immunology, and Pathology, Colorado State University, 1682 Campus Delivery, Fort Collins, CO 80523, United States.
authors: Steven J
authors: SJ
authors: Woods
authors: Division of Pathology, National Jewish Health, Denver, CO, United States.
authors: Steven D
authors: SD
authors: Groshong
authors: Department of Microbiology, Immunology, and Pathology, Colorado State University, 1682 Campus Delivery, Fort Collins, CO 80523, United States.
authors: Randall J
authors: RJ
authors: Basaraba
authors: Department of Physiology, School of Medicine, John Hopkins University, Baltimore, MD, United States.
authors: John M
authors: JM
authors: Gilchrist
authors: School of Medicine, University of Colorado, Health Sciences Center, Denver, CO, United States.
authors: David M
authors: DM
authors: Higgins
authors: Department of Microbiology, Immunology, and Pathology, Colorado State University, 1682 Campus Delivery, Fort Collins, CO 80523, United States.
authors: Mercedes
authors: M
authors: Gonzalez-Juarrero
authors: Histology Core Services, Veterinary Teaching Hospital, Colorado State University, Fort Collins, CO, United States.
authors: Todd A
authors: TA
authors: Bass
authors: Department of Pathology, Northwestern University, Chicago, IL, United States.
authors: William A
authors: WA
authors: Muller
authors: Department of Microbiology, Immunology, and Pathology, Colorado State University, 1682 Campus Delivery, Fort Collins, CO 80523, United States.
authors: Alan R
authors: AR
authors: Schenkel
mesh_terms: D000818:Animals; D001760:Bleeding Time; D004195:Disease Models, Animal; D005337:Fibrin / Q000378:metabolism; D006470:Hemorrhage / Q000378:metabolism / Q000473:pathology*; D006485:Hemosiderin / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D058628:Myofibroblasts / Q000473:pathology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism*; D011658:Pulmonary Fibrosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*
chemical_list: C556062:IL10 protein, mouse; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D016753:Interleukin-10; D005337:Fibrin; D006485:Hemosiderin
keywords: Interstitial fibrosis; Macrophage biology; Pulmonary oedema