Keratinocyte growth factor and hepatocyte growth factor/scatter factor are heparin-binding growth factors for alveolar type II cells in fibroblast-conditioned medium.

Panos, Ralph J.; Rubin, Jeffrey S.; Csaky, Karl G.; Aaronson, S A; Mason, Robert J.

doi:10.1172/jci116673

Cited by 285 publications

(183 citation statements)

References 62 publications

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“…In the present experiments, the same recombinant VEGF at the same concentrations failed to induce any increase in thymidine or BrdU incorporation in isolated type II cells, which, by contrast, responded strongly to KGF, consistent with previous findings in adult (26,35) as well as fetal (7) type II cells. Our findings, therefore, suggest that the proliferative effects of VEGF previously observed in lung explants were indirect.…”

Section: Discussionsupporting

confidence: 93%

Effects of vascular endothelial growth factor on isolated fetal alveolar type II cells

Raoul¹,

Chailley‐Heu²,

Barlier-Mur³

et al. 2004

American Journal of Physiology-Lung Cellular and Molecular Phys

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Previous investigations gained from in vivo or lung explant studies suggested that VEGF is an autocrine proliferation and maturation factor for developing alveolar type II cells. The objective of this work was to determine whether VEGF exerted its growth and maturation effects directly on isolated type II cells. These were isolated from 19-day fetal rat lung and cultured in defined medium. The presence of VEGF receptor-2 was assessed in cultured cells at the pre- and posttranslational levels. Recombinant VEGF165, formerly found to be active on lung explants, failed to enhance type II cell proliferation estimated by thymidine and 5-bromo-2′-deoxy-uridine incorporation. It increased choline incorporation in saturated phosphatidylcholine by 27% but did not increase phospholipid surfactant pool size. VEGF (100 ng/ml) left unchanged the transcript level of surfactant proteins (SP)-A, SP-C, and SP-D but increased SP-B transcripts to four times the control steady-state level. VEGF slightly retarded, but did not prevent, the in vitro transdifferentiation of type II into type I cells, as assessed by immunolabeling of the type I cell marker T1α. We conclude that, with the exception of SP-B expression, which appears to be controlled directly, the previously observed effects of this VEGF isoform on type II cells are likely to be exerted indirectly through reciprocal paracrine interactions involving other lung cell types.

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Section: Discussionsupporting

confidence: 93%

Effects of vascular endothelial growth factor on isolated fetal alveolar type II cells

Raoul¹,

Chailley‐Heu²,

Barlier-Mur³

et al. 2004

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…However, rat serum increases the proliferative effects of KGF. In an earlier study (33), it was noted that FBS was required for the effect of KGF on thymidine incorporation. Clearly, additional studies on the interaction between rat serum and KGF are warranted; however, they are beyond the scope of this report.…”

Section: Discussionmentioning

confidence: 96%

“…The growth factors and the concentrations used were chosen based on the ability to stimulate thymidine incorporation by adult rat type II cells (24,27,33). As shown in Fig.…”

Section: Effect Of Kgf Without Fibroblasts On Sp-a and Sp-d Secretionmentioning

confidence: 99%

“…Therefore, the fibroblasts were plated in a collagen gel on the underside of the matrix-coated filter. To prevent fibroblast proliferation and gel contraction, the fibroblasts were treated with 10 g/ml of mitomycin C for 2 h. Early-passage human lung fibroblasts were used be-cause these were a known source of HGF and KGF and have been used in our previous studies (33). Type II cells were plated in medium containing 10% FBS for 24 h to promote attachment, and then the medium was changed to DMEM with 1% CS-FBS.…”

Section: Effect Of Kgf Without Fibroblasts On Sp-a and Sp-d Secretionmentioning

confidence: 99%

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Maintenance of surfactant protein A and D secretion by rat alveolar type II cells in vitro

Mason

Lewis

Edeen

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

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Secretion of surfactant proteins A and D (SP-A and SP-D) has been difficult to study in vitro because a culture system for maintaining surfactant secretion has been difficult to establish. We evaluated several growth factors, corticosteroids, rat serum, and a fibroblast feeder layer for the ability to produce and maintain a polarized epithelium of type II cells that secretes SP-A and SP-D into the apical medium. Type II cells were plated on a filter insert coated with an extracellular matrix and were cultured at an air-liquid interface. Keratinocyte growth factor (KGF) stimulated type II cell proliferation and secretion of SP-A and SP-D more than fibroblast growth factor-10 (FGF-10), hepatocyte growth factor (HGF), or heparin-binding epidermal-like growth factor (HB-EGF). Cells cultured in the presence of KGF and rat serum with or without fibroblasts had high surfactant protein mRNA levels and exhibited a high level of SP-A and SP-D secretion. Dexamethasone inhibited type II cell proliferation but increased expression of SP-B. In the presence of KGF, rat serum, and dexamethasone, the mRNAs for the surfactant proteins were maintained at high levels. Secretion of SP-A and SP-D was found to be independent of phospholipid secretion.

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“…The role of IL-1β in epithelial repair also appears to be mediated by EGF and TGF-α, as blockade of this pathway abrogates epithelial cell migration in vitro [96]. KGF has been shown to induce alveolar type II proliferation in vitro and in vivo, and it reduces disease severity and mortality of murine models of ALI [100][101][102][103][104][105][106][107]. It also appears to function through a common pathway via EGFR [97].…”

Section: Epithelial Cell Repairmentioning

confidence: 99%

Role of the pulmonary epithelium and inflammatory signals in acute lung injury

Manicone¹

2009

Expert Review of Clinical Immunology

113

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Acute lung injury (ALI) is a clinical disease marked by respiratory failure due to disruption of the epithelial and endothelial barrier, flooding of the alveolar compartment with protein-rich fluid and recruitment of neutrophils into the alveolar space. ALI affects approximately 200,000 patients annually in the USA and results in approximately 75,000 deaths. It is associated with prolonged mechanical ventilation, intensive medical care, high morbidity and mortality, and rising healthcare costs. Owing to its impact on public health, great strides have been made towards understanding the pathobiology of ALI to affect outcome. This review will focus on the role of the epithelial cell in the pathogenesis and resolution of ALI and the role of various inflammatory mediators in ALI. Keywordsβ2-agonist; acute lung injury; acute respiratory distress syndrome; chemokine; cytokine; epithelial cell; inflammation; methylprednisolone; neutrophil; salbutamol; steroid; ventilator-induced lung injuryAcute lung injury/acute respiratory distress syndrome (ALI/ARDS) was first described in 1967 by Ashbaugh and colleagues in a group of 12 patients who shared a constellation of clinical symptoms including acute respiratory distress, hypoxemia refractory to supplemental oxygen, decreased lung compliance and diffuse pulmonary infiltrates [1]. Since this first description, the clinical criteria have evolved to include acute onset of respiratory distress, bilateral pulmonary infiltrates seen on chest radiographs, absence of left-sided heart failure and hypoxemia, with the severity of hypoxemia distinguishing ALI and ARDS (Box 1) [2]. Extrapolating from recent epidemiologic studies using these criteria, ALI affects about 200,000 patients annually in the USA and results in approximately 75,000 deaths [3]. This disease, which can be caused by common events such as pneumonia, sepsis and trauma, results in high morbidity, mortality and healthcare expenditures associated with prolonged mechanical ventilation and intensive care. Because of its impact on public health and patient outcomes, great strides have been made towards understanding the pathobiology of ALI.When defined broadly to include all processes related to defense against microbes, other environmental insults and injury, a wide variety of cell types and proteins participate in inflammation and immunity. Leukocytes are the paradigmatic inflammatory cell type, but they are not the only cells that function in defense and immunity. The epithelial lining of all tissues forms a continuous barrier to the environment and is the first line of defense against infectious agents and toxins. Though specialized to serve distinct functions among tissues, epithelial cells respond similarly to injury and infection, and regulate leukocyte influx through the production of proinflammatory cytokines, chemokines and other factors that modulate chemokine gradients and effect leukocyte migration. This review will focus on the role of the pulmonary epithelium and inflammatory mediators in ALI. More s...

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Keratinocyte growth factor and hepatocyte growth factor/scatter factor are heparin-binding growth factors for alveolar type II cells in fibroblast-conditioned medium.

Abstract: IntroductionEpithelial-mesenchymal interactions mediate aspects of normal lung growth and development and are important in the restoration of normal alveolar architecture after lung injury.

Cited by 285 publications

References 62 publications

Effects of vascular endothelial growth factor on isolated fetal alveolar type II cells

Effects of vascular endothelial growth factor on isolated fetal alveolar type II cells

Maintenance of surfactant protein A and D secretion by rat alveolar type II cells in vitro

Role of the pulmonary epithelium and inflammatory signals in acute lung injury

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