A quantitative ultrastructural study of circulating (monocytic) cells interacting with endothelial cells in high oxygen-injured and spontaneously re-forming (FVB) mouse lung capillaries

Harvard Medical School, Department of Anesthesia, Critical Care and Pain Management, Massachusetts General Hospital, Boston, MA, USA.
Ultrastructural Pathology (Impact Factor: 1.08). 08/2012; 36(4):260-79. DOI: 10.3109/01913123.2012.662820
Source: PubMed


The present study demonstrates the fine structure of blood-borne (monocytic) circulating cells (CCs), and their interaction with endothelial cells, in a mouse model of lung capillary injury and repair. Quantitative analysis highlights the diversity of CC profiles entering the lung, where they form contact and adhesion/fusion sites to endothelial plasmalemmal membranes, and to complexes of endothelial/basement membrane remnants, as capillary networks reorganize over time. Temporal patterns of CC influx and efflux in the lung, changing CC phenotypes, and the range of CC interactions with endothelium, underscore the potential for a complex angiogenic/immunogenic response, as capillary networks stabilize and undergo expansion and growth.

2 Reads
    • "The expression of CXCR4 by the circulating monocytic cells, and of CXCL12 by adjacent endothelial cells, demonstrates a mechanism for retention of these cells at the capillary surface. Myeloid VEGF receptor-2 þ CD11b þ precursors are identified within the circulating monocytic cell population (Jones and Capen, 2012, 2014). In previous studies we demonstrated the presence of endothelial cells expressing CXCL12 and stromal cells expressing CXCR4 and VEGF receptor-2 in fibrovascular epiretinal membranes from patients with PDR (Abu El-Asrar et al., 2010, 2011). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Myofibroblasts expressing α-smooth muscle actin (α-SMA) are the key cellular mediator of fibrosis. Fibrovascular epiretinal membranes from patients with proliferative diabetic retinopathy (PDR) are characterized by the accumulation of a large number of myofibroblasts. We explored the hypothesis that proliferating endothelial cells via endothelial-to-mesenchymal transition (EndoMT) and/or bone marrow-derived circulating fibrocytes contribute to the myofibroblast population present in PDR epiretinal membranes. Epiretinal membranes from 14 patients with PDR were studied by immunohistochemistry. All membranes contained neovessels expressing the endothelial cell marker CD31. CD31+ endothelial cells co-expressed the fibroblast/myofibroblast markers fibroblast-specific protein-1 (FSP-1) and α-SMA, indicative for the occurrence of endoMT. In the stroma, cells expressing FSP-1, α-SMA, the leukocyte common antigen CD45, and the myelomonocytic marker CD11b were detected. Double labeling showed co-localization of CD45 with FSP-1 and α-SMA and co-localization of CD11b with α-SMA and matrix metalloproteinase-9, demonstrating the presence of infiltrating fibrocytes. In addition, we investigated the phenotypic changes that take place in human retinal microvascular endothelial cells following exposure to transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF) and the proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Retinal microvascular endothelial cells changed morphology upon cytokine exposure, lost the expression of endothelial cell markers (endothelial nitric oxide synthase and vascular endothelial-cadherin) and started to express mesenchymal markers (calponin, snail, transgelin and FSP-1). These results suggest that endothelial cells as well as circulating fibrocytes may differentiate into myofibroblasts in the diabetic eye and contribute to pathologic fibrosis in PDR.
    No preview · Article · Jan 2015 · Experimental Eye Research
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract The present study provides new insight into structural processes remodeling pulmonary capillaries in adult lung. The data highlight mechanisms underlying the expansion and increased density of capillary segments on return to air breathing (FiO2 0.21) after injury in high oxygen (FiO2 0.75). As segments expand and increase in number, endothelial cells extend their processes to bridge the lumen and support the walls of developing interluminal structures (ILSs); endothelial-epithelial surfaces infold as a single unit (sheet) into the lumen, increasing the length of each surface and subdividing segments by loop formation and by the formation of ILSs; segments further increase in number as lumen subdivision proceeds by intussusceptive microvascular growth (IMG).
    No preview · Article · Oct 2013 · Ultrastructural Pathology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract The present study demonstrates the fine structure of pulmonary capillaries first injured and then undergoing growth in response to a change in the ambient alveolar oxygen tension. Breathing a high fraction of inspired oxygen (FiO2 0.75) triggers restriction by endothelial cell injury and effacement leading to segment narrowing and shortening and segment loss as demonstrated by a fall in density. Subsequently, breathing a relatively low fraction (FiO2 0.21) triggers capillary assembly (angiogenesis), which reverses the changes. The data underscore the structural reprogramming (reduction and restoration) of pulmonary capillaries in response to significant shifts in oxygen tension.
    No preview · Article · Oct 2013 · Ultrastructural Pathology
Show more