Age and sex dimorphisms contribute to the severity of bleomycin-induced lung injury and fibrosis

Redente, Elizabeth F.; Jacobsen, Kristen M.; Solomon, Joshua J.; Lara, Abigail; Sarah, Faubel; Keith, Rebecca C.; Henson, Peter M.; Downey, Gregory P.; Riches, David W. H.

doi:10.1152/ajplung.00122.2011

Cited by 151 publications

(153 citation statements)

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“…Both NO and CO diffusing capacities are decreased, much more in the BLM group. However, in animals, BLM-induced lung injury and �brosis are known to be more serious in males than in females [28]. So, the greater proportion of females in the N and MTX groups could induce a bias.…”

Section: Discussionmentioning

confidence: 99%

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Combined Lung Transfer of NO and CO in Patients Receiving Methotrexate or Bleomycin Therapy Compared to Normal Subjects

et al. 2013

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e �rst aim of the study is to determine whether combined lung diffusing capacities of nitric oxide (TLNO) and of carbon monoxide (TLCO) are accurate in the followup of patients receiving either methotrexate (MTX) or bleomycin (BLM). e second objective is to determine whether TLCO, TLNO, KCO, and TLCO/VI% (inspiratory volume expressed as percentage of predicted value) correlate better with the diffusing capacity of the membrane (Dm) and/or capillary lung volume (Vc). TLNO and TLCO were measured in three groups: 22 "normal" subjects (N group), 17 patients receiving MTX, and 12 patients treated with BLM. TLCO, TLNO, Dm, and Vc were much lower in the MTX and BLM groups compared to those of the N one. e ratio TLNO/TLCO was higher in the BLM group compared to that of the N group and compared to that of the MTX group. KCO correlated neither with Dc nor with Vc, whereas TLCO/VI% correlated signi�cantly with both Dm and Vc. Combined measurement of TLCO and TLNO seems to be useful in the followup of patients receiving agents inducing lung toxicity and gives a good idea of the alveolar membrane and the capillary volume.

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Section: Discussionmentioning

confidence: 99%

“…Bleomycin (BLM) is another agent known for its pulmonary toxicity [8][9][10][11][12][13]. is cytotoxic agent is successfully used in the treatment of several malignancies such as germ cell tumors, lymphomas, and some squamous cell carcinomas.…”

Section: Introductionmentioning

confidence: 99%

Combined Lung Transfer of NO and CO in Patients Receiving Methotrexate or Bleomycin Therapy Compared to Normal Subjects

et al. 2013

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“…49 Finally, MMP-3-defi cient mice were protected from bleomycin-induced pulmonary fi brosis, 50 a model that includes an early acute infl ammatory response associated with ALI. 51 While the mechanisms by which MMPs induce neutrophil recruitment into the lung remain unclear, several possibilities can be inferred from studies investigating their roles in disease models of the lung and other organs. For example, MMP-7 released from wounded epithelial cells cleaves a complex of KC/syndecan-1, allowing the complex to cross the epithelium into the alveolar space and establish a chemotactic gradient for neutrophils.…”

Section: Mmp Levels Correlate With Risk and Severity Of Ards In Humansmentioning

confidence: 99%

Matrix Metalloproteinases and Protein Tyrosine Kinases

Aschner

Zemans

Yamashita

et al. 2014

CHEST

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Acute lung injury (ALI) and ARDS fall within a spectrum of pulmonary disease that is characterized by hypoxemia, noncardiogenic pulmonary edema, and dysregulated and excessive infl ammation. While mortality rates have improved with the advent of specialized ICUs and lung protective mechanical ventilation strategies, few other therapies have proven eff ective in the management of ARDS, which remains a signifi cant clinical problem. Further development of biomarkers of disease severity, response to therapy, and prognosis is urgently needed.Several novel pathways have been identifi ed and studied with respect to the pathogenesis of ALI and ARDS that show promise in bridging some of these gaps. This review will focus on the roles of matrix metalloproteinases and protein tyrosine kinases in the pathobiology of ALI in humans, and in animal models and in vitro studies. These molecules can act independently, as well as coordinately, in a feed-forward manner via activation of tyrosine kinase-regulated pathways that are pivotal in the development of ARDS. Specifi c signaling events involving proteolytic processing by matrix metalloproteinases that contribute to ALI, including cytokine and chemokine activation and release, neutrophil recruitment, transmigration and activation, and disruption of the intact alveolar-capillary barrier, will be explored in the context of these novel molecular pathways.CHEST 2014; 146 (4): 1081 -1091 ABBREVIATIONS : ALI 5 acute lung injury ; ECM 5 extracellular matrix ; EGFR 5 epidermal growth factor receptor ; LPS 5 lipopolysaccharide ; MMP 5 matrix metalloproteinase ; NRTK 5 nonreceptor tyrosine kinase ; PDGF 5 platelet-derived growth factor ; PDGFR 5 platelet-derived growth factor receptor ; PTK 5 protein tyrosine kinase ; RTK 5 receptor tyrosine kinase ; SFK 5 Src family kinase ; VEGF 5 vascular endothelial growth factor ; VEGFR 5 vascular endothelial growth factor receptor ; VILI 5 ventilatorinduced lung injury Manuscript

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“…In the past, most experimental studies have been conducted in rodents aged 6-12 weeks, the equivalent of about 10-12 years in humans [55]. A recent study was performed with bleomycin instilled intratracheally to young (8-12 weeks) and aged (52-54 weeks) male and female C57BL/6 mice [56]. In this model, aged male mice developed more severe lung disease with increased mortality compared to young mice [56] and young male mice developed more pulmonary fibrosis than young female mice [56,57], demonstrating that both advanced age and male sex contribute to fibrotic pathophysiology in the animal model.…”

Section: Ipf Is a Disease Of Ageingmentioning

confidence: 99%

“…A recent study was performed with bleomycin instilled intratracheally to young (8-12 weeks) and aged (52-54 weeks) male and female C57BL/6 mice [56]. In this model, aged male mice developed more severe lung disease with increased mortality compared to young mice [56] and young male mice developed more pulmonary fibrosis than young female mice [56,57], demonstrating that both advanced age and male sex contribute to fibrotic pathophysiology in the animal model. Furthermore, mice prone to accelerated senescence are also more susceptible to bleomycin-induced pulmonary fibrosis compared to control mice [58].…”

Section: Ipf Is a Disease Of Ageingmentioning

confidence: 99%

Neglected evidence in idiopathic pulmonary fibrosis: from history to earlier diagnosis

Cordier¹,

Cottin²

2013

Eur Respir J

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This perspective highlights some evidence that has hitherto been neglected, especially because it may not have been sufficiently explicated in the clinical respiratory medicine literature. Idiopathic pulmonary fibrosis (IPF) has appeared only in the second half of the 20th century and, like lung cancer and chronic obstructive pulmonary disease, may be a direct consequence of the cigarette smoking epidemic. It is a disease of lung ageing, with most affected patients being .70 years of age. The relationship between lung ageing and pulmonary fibrosis is further illustrated in the bleomycin mouse model, in which older males develop more fibrosis than young female mice.Earlier diagnosis of IPF is a prerequisite for significant progress to be made in the long-term outcome and prognosis. We consider that only two different yet complementary and realistic approaches could lead to earlier diagnosis of IPF and possibly to allowing more efficient disease management: 1) investigating any patients with early Velcro crackles at lung auscultation through proactive education of, and commitment from, primary care physicians; and 2) using current large-scale lung cancer screening strategies with lowdose high-resolution computed tomography in smokers for the detection of subclinical interstitial lung disease and especially early IPF. @ERSpublications Only two approaches could lead to earlier diagnosis of IPF and more efficient disease management

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Age and sex dimorphisms contribute to the severity of bleomycin-induced lung injury and fibrosis

Abstract: Redente EF, Jacobsen KM, Solomon JJ, Lara AR, Faubel S, Keith RC, Henson PM, Downey GP, Riches DW. Age and sex dimorphisms contribute to the severity of bleomycin-induced lung injury and fibrosis.

Cited by 151 publications

References 58 publications

Combined Lung Transfer of NO and CO in Patients Receiving Methotrexate or Bleomycin Therapy Compared to Normal Subjects

Combined Lung Transfer of NO and CO in Patients Receiving Methotrexate or Bleomycin Therapy Compared to Normal Subjects

Matrix Metalloproteinases and Protein Tyrosine Kinases

Neglected evidence in idiopathic pulmonary fibrosis: from history to earlier diagnosis

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