Neutrophil gelatinase-associated lipocalin in idiopathic pulmonary fibrosis

Ikezoe, Kohei; Handa, Tomohiro; Mori, Kiyoshi; Watanabe, Kizuku; Tanizawa, Kiminobu; Aihara, Kensaku; Tsuruyama, Tatsuaki; Miyagawa‐Hayashino, Aya; Sokai, Akihiko; Kubo, Takeshi; Muro, Shigeo; Nagai, Sonoko; Hirai, Toyohiro; Chin, Kazuo; Mishima, Michiaki

doi:10.1183/09031936.00192613

Cited by 13 publications

(16 citation statements)

References 9 publications

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“…14,18 Beyond its effects on tumor cells, LCN2 expression has also been implicated as a mediator of renal, pulmonary, and cardiac fibrosis. [32][33][34] In this study, we showed that the levels of LCN2 in the plasmas of MF patients (PMF, PV-MF, and ET-MF) were greater than those present in normal control plasma, findings that extend the observations of others. [10][11][12][13] Furthermore, the LCN2 levels present in the MF plasmas were two-to threefold greater than those observed in patients with proliferative MPNs (PV and ET), providing a possible link between increased LCN2 levels and progression to MF.…”

Section: Discussionsupporting

confidence: 75%

Lipocalin produced by myelofibrosis cells affects the fate of both hematopoietic and marrow microenvironmental cells

Lü

Xia

Liu

et al. 2015

Blood

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Key Points• LCN2 acts to generate reactive oxygen species, leading to increased DNA strand breaks and apoptosis in normal CD34 1 cells.• LCN2 promotes the generation of osteoblasts but diminishes adipogenesis, resembling the composition of the MF marrow microenvironment.Myelofibrosis (MF) is characterized by cytopenias, constitutional symptoms, splenomegaly, and marrow histopathological abnormalities (fibrosis, increased microvessel density, and osteosclerosis). The microenvironmental abnormalities are likely a consequence of the elaboration of a variety of inflammatory cytokines generated by malignant megakaryocytes and monocytes. We observed that levels of a specific inflammatory cytokine, lipocalin-2 (LCN2), were elevated in the plasmas of patients with myeloproliferative neoplasms (MF > polycythemia vera or essential thrombocythemia) and that LCN2 was elaborated by MF myeloid cells. LCN2 generates increased reactive oxygen species, leading to increased DNA strand breaks and apoptosis of normal, but not MF, CD34 1 cells. Furthermore, incubation of marrow adherent cells or mesenchymal stem cells with LCN2 increased the generation of osteoblasts and fibroblasts, but not adipocytes. LCN2 priming of mesenchymal stem cells resulted in the upregulation of RUNX2 gene as well as other genes that are capable of further affecting osteoblastogenesis, angiogenesis, and the deposition of matrix proteins. These data indicate that LCN2 is an additional MF inflammatory cytokine that likely contributes to the creation of a cascade of events that results in not only a predominance of the MF clone but also a dysfunctional microenvironment. (Blood. 2015;126(8):972-982)

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Section: Discussionsupporting

confidence: 75%

Lipocalin produced by myelofibrosis cells affects the fate of both hematopoietic and marrow microenvironmental cells

Lü

Xia

Liu

et al. 2015

Blood

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“…Although NGAL is extensively studied in renal diseases, recent studies have suggested that NGAL levels in the blood or bronchoalveolar lavage fluid can reflect disease severity in many pulmonary diseases such as COPD and IPF (Betsuyaku et al 1999;Eagan et al 2010;Ikezoe et al 2014). Compared with controls, COPD patients were more likely to exhibit higher levels of NGAL, and elevated NGAL level was significantly associated with severe disease progression (i.e., more frequent exacerbations) (Eagan et al 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Regarding pulmonary diseases, it has been suggested that blood or bronchoalveolar lavage fluid NGAL may reflect inflammation in many pulmonary diseases such as chronic obstructive pulmonary disease (COPD) (Betsuyaku et al 1999;Eagan et al 2010), idiopathic pulmonary fibrosis (IPF) (Ikezoe et al 2014), and ventilator-associated lung injury (Xiao and Chen 2017).…”

Section: Introductionmentioning

confidence: 99%

Neutrophil Gelatinase-Associated Lipocalin for Predicting Intensive Care Unit Admission and Mortality in Patients with Pneumonia

Min

Lee

Chung

et al. 2020

Tohoku J. Exp. Med.

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Pneumonia is one of the most common causes of hospital admissions and mortality, and it is responsible for significant socioeconomic burden worldwide. Neutrophil gelatinase-associated lipocalin (NGAL) is a 25-kDa protein, which is involved in iron trafficking and has chemostatic and bacteriostatic effects. NGAL is also known as an early marker of many inflammatory diseases. However, little is known about the role of NGAL in the management of pneumonia. Thus, this study aimed to investigate whether plasma NGAL levels can predict intensive care unit (ICU) admission and in-hospital mortality in patients with pneumonia. This retrospective observational study included 241 adults hospitalized with pneumonia who underwent NGAL measurement. We compared the prognostic values of plasma NGAL with pneumonia severity index (PSI) for prediction of ICU admission and in-hospital mortality. Of 241 patients, 47 (19.5%) died during hospital admission. There was no significant difference between NGAL and PSI for predicting ICU admission (area under the receiver operating characteristic curve [AUC] of log NGAL vs. PSI, P > 0.999). Although log NGAL was useful in predicting in-hospital mortality, its ability was inferior to that of PSI (AUC of log NGAL vs. PSI, P = 0.008). Multivariable analysis revealed that log NGAL was significantly associated with ICU admission (adjusted odds ratio = 10.76, P < 0.001) and in-hospital mortality (adjusted odds ratio = 5.04, P = 0.004). These results suggest that plasma NGAL level is a useful biomarker for predicting ICU admission and mortality in hospitalized patients with pneumonia.

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“…In line with our findings in IPF are correlations of Lipocalin-2 BAL levels with BAL neutrophilia and forced vital capacity, as well as no elevation of plasma Lipocalin-2. Further, Lipocalin-2 was expressed in airway epithelial cells that covered the honeycomb cysts and in bronchioles of IPF patients 21 .…”

Section: Discussionmentioning

confidence: 95%

Potential novel biomarkers for chronic lung allograft dysfunction and azithromycin responsive allograft dysfunction

Veraar

Kliman

Benazzo

et al. 2021

Sci Rep

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Chronic Lung Allograft Dysfunction (CLAD), manifesting as Bronchiolitis Obliterans Syndrome (BOS) or Restrictive Allograft Syndrome (RAS), is the main reason for adverse long-term outcome after Lung Transplantation (LTX). Until now, no specific biomarkers exist to differentiate between CLAD phenotypes. Therefore, we sought to find suitable cytokines to distinguish between BOS, RAS and Azithromycin Responsive Allograft Dysfunction (ARAD); and reveal potential similarities or differences to end-stage fibrotic diseases. We observed significantly increased Lipocalin-2 serum concentrations in RAS compared to BOS patients. In addition, in RAS patients immunohistochemistry revealed Lipocalin-2 expression in bronchial epithelium and alveolar walls. Patients with ARAD showed significantly lower Activin-A serum concentrations compared to Stable-LTX and BOS patients. Further, increased serum concentrations of Lipocalin-2 and Activin-A were predictors of worse freedom-from-CLAD in Stable-LTX patients. These biomarkers serve as promising serum biomarkers for CLAD prediction and seem suitable for implementation in clinical practice.

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Neutrophil gelatinase-associated lipocalin in idiopathic pulmonary fibrosis

Cited by 13 publications

References 9 publications

Lipocalin produced by myelofibrosis cells affects the fate of both hematopoietic and marrow microenvironmental cells

Lipocalin produced by myelofibrosis cells affects the fate of both hematopoietic and marrow microenvironmental cells

Neutrophil Gelatinase-Associated Lipocalin for Predicting Intensive Care Unit Admission and Mortality in Patients with Pneumonia

Potential novel biomarkers for chronic lung allograft dysfunction and azithromycin responsive allograft dysfunction

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