Normal function and lack of fibronectin accumulation in kidneys of Clara cell secretory protein/uteroglobin deficient mice

Reynolds, Susan D.; Mango, G; Gelein, Robert; Bøe, Inger-Margrethe; Lund, Johan; Stripp, Barry R.

doi:10.1016/s0272-6386(99)70192-7

Cited by 21 publications

(26 citation statements)

References 48 publications

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“…This is presumed to be secondary to CCSP inhibiting PLA 2 activity. This PLA 2 inhibition has been implicated in CCSP reducing integrin activation and subsequent abnormal fibronectin deposition and fibroblast migration (21,35). This supports the findings in our model of increased injury associated with declining CCSP levels.…”

Section: Discussionsupporting

confidence: 90%

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Club cell secretory protein improves survival in a murine obliterative bronchiolitis model

Wendt

Tram

Price

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

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Club cell secretory protein (CCSP) is an indirect phospholipase A2 inhibitor with some immunosuppressive and antiproliferative properties that is expressed in bronchiolar Club cells. In our murine bone marrow transplant (BMT) model of obliterative bronchiolitis (OB), CCSP is diminished; however, its role is unknown. To determine the role of CCSP, B6 wild-type (WT) or CCSP-deficient (CCSP(-/-)) mice were lethally conditioned and given allogeneic bone marrow with a sublethal dose of allogeneic splenic T cells to induce OB. We found that CCSP(-/-) mice demonstrated a higher mortality following BMT-induced OB compared with WT mice. Mice were analyzed 60 days post-BMT for protein expression, pulmonary function, and histology. CCSP levels were reduced in WT mice with BMT-induced OB, and lower levels correlated to decreased lung compliance. CCSP(-/-) had a higher degree of injury and fibrosis as measured by hydroxy proline, along with an increased lung resistance and the inflammatory markers, leukotriene B4 and CXCL1. Replacement with recombinant intravenous CCSP partially reversed the weight loss and improved survival in the CCSP(-/-) mice. In addition, CCSP replacement improved histology and decreased inflammatory cells and markers. These findings indicate that CCSP has a regulatory role in OB and may have potential as a preventive therapy.

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Section: Discussionsupporting

confidence: 90%

“…Specifically, CCSP has potent immunosuppressor and anti-inflammatory roles while promoting wound healing through fibroblast migration (5,21). In vitro, CCSP inhibits both monocyte and neutrophil chemotaxis in a dose-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

Club cell secretory protein improves survival in a murine obliterative bronchiolitis model

Wendt

Tram

Price

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…44,45 The absence of immunoreactivity on this tissue indicated that the rabbit and goat anti-CCSP antibodies are specific to CCSP and that there are no antigens within neuroepithelial cells that cross-react with this antibody. The rabbit anti-CGRP primary antibodies detect rare clusters of cells located primarily at branch points and walls opposite bifurcations and scattered single cells in untreated lung tissue.…”

Section: Immunohistochemistrymentioning

confidence: 96%

Neuroepithelial Bodies of Pulmonary Airways Serve as a Reservoir of Progenitor Cells Capable of Epithelial Regeneration

Reynolds

Giangreco

Power

et al. 2000

The American Journal of Pathology

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401

330

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Remodeling of the conducting airway epithelium is a common finding in the chronically injured lung and has been associated with increased risk for developing lung cancer. Pulmonary neuroendocrine cells and clusters of these cells termed neuroepithelial bodies (NEBs) play a central role in each of these processes. We previously developed an adult mouse model of airway injury and repair in which epithelial regeneration after naphthalene-induced Clara cell ablation occurred preferentially at airway branch points and gave rise to nascent Clara cells. Continued repair was accompanied by NEB hyperplasia. We now provide the following evidence that the NEB microenvironment serves as a source of airway progenitor cells that contribute to focal regeneration of the airway epithelium: 1) nascent Clara cells and NEBs localize to the same spatial domain; 2) within NEB , both Clara cell secretory protein-and calcitonin gene-

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“…Standard immunohistochemical techniques were used. 34 Rabbit anti-rat CCSP was used as previously described. 16 Mouse monoclonal K14 antibody (Clone LL002, 35) was purchased from NeoMarkers (Fremont, CA) and is specific for the highly conserved carboxy-terminal 16-amino acids of K14.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Basal Cells Are a Multipotent Progenitor Capable of Renewing the Bronchial Epithelium

Hong

Reynolds

Watkins

et al. 2004

The American Journal of Pathology

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475

390

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Commitment of the pulmonary epithelium to bronchial and bronchiolar airway lineages occurs during the transition from pseudoglandular to cannalicular phases of lung development, suggesting that regional differences exist with respect to the identity of stem and progenitor cells that contribute to epithelial maintenance in adulthood. We previously defined a critical role for Clara cell secretory protein-expressing (CE) cells in renewal of bronchiolar airway epithelium following injury. Even though CE cells are also the principal progenitor for maintenance of the bronchial airway epithelium, CE cell injury is resolved through a mechanism involving recruitment of a second progenitor cell population that we now identify as a GSI-B 4 reactive, cytokeratin-14-expressing basal cell. These cells exhibit multipotent differentiation capacity as assessed by analysis of cellular phenotype within clones of LacZ-tagged cells. Clones were derived from K14-expressing cells tagged in a cell-type-specific fashion by ligand-regulable Cre recombinase-mediated genomic rearrangement of the ROSA26 recombination substrate allele. We conclude that basal cells represent an alternative multipotent progenitor cell population of bronchial airways and that progenitor cell selection is dictated by the type of airway injury. Conducting airways of the lung are lined by a highly specialized epithelium whose composition and function varies along the proximal to distal axis. Despite a growing appreciation of mechanisms contributing to branching morphogenesis and lineage specification in the developing lung it is still unclear how a complex epithelium such as that present in the conducting airway is established and maintained through adulthood. Studies in the developing rat lung indicate that lineage restriction occurs during the transition from the pseudoglandular to cannalicular phases of lung development. At this time cells of the proximal airway lose the ability to respond to mesenchymally derived signals capable of inducing distal airway differentiation.

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Normal function and lack of fibronectin accumulation in kidneys of Clara cell secretory protein/uteroglobin deficient mice

Cited by 21 publications

References 48 publications

Club cell secretory protein improves survival in a murine obliterative bronchiolitis model

Club cell secretory protein improves survival in a murine obliterative bronchiolitis model

Neuroepithelial Bodies of Pulmonary Airways Serve as a Reservoir of Progenitor Cells Capable of Epithelial Regeneration

Basal Cells Are a Multipotent Progenitor Capable of Renewing the Bronchial Epithelium

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