Differential modulation of surfactant protein D under acute and persistent hypoxia in acute lung injury

2012 ◽  
Vol 303 (1) ◽  
pp. L43-L53 ◽  
Author(s):  
Koji Sakamoto ◽  
Naozumi Hashimoto ◽  
Yasuhiro Kondoh ◽  
Kazuyoshi Imaizumi ◽  
Daisuke Aoyama ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Acute Hypoxia ◽  
Surfactant Protein ◽  
Surfactant Protein D ◽  
Alveolar Cells ◽  
Mesenchymal Transition ◽  
Twist Expression

Hypoxia contributes to the development of fibrosis with epithelial-mesenchymal transition (EMT) via stimulation of hypoxia-inducible factor 1α (HIF-1α) and de novo twist expression. Although hypoxemia is associated with increasing levels of surfactant protein D (SP-D) in acute lung injury (ALI), the longitudinal effects of hypoxia on SP-D expression in lung tissue injury/fibrosis have not been fully evaluated. Here, the involvement of hypoxia and SP-D modulation was evaluated in a model of bleomycin-induced lung injury. We also investigated the molecular mechanisms by which hypoxia might modulate SP-D expression in alveolar cells, by using a doxycycline (Dox)-dependent HIF-1α expression system. Tissue hypoxia and altered SP-D levels were present in bleomycin-induced fibrotic lesions. Acute hypoxia induced SP-D expression, supported by the finding that Dox-induced expression of HIF-1α increased SP-D expression. In contrast, persistent hypoxia repressed SP-D expression coupled with an EMT phenotype and twist expression. Long-term expression of HIF-1α caused SP-D repression with twist expression. Ectopic twist expression repressed SP-D expression. The longitudinal observation of hypoxia and SP-D levels in ALI in vivo was supported by the finding that HIF-1α expression stabilized by acute hypoxia induced increasing SP-D expression in alveolar cells, whereas persistent hypoxia induced de novo twist expression in these cells, causing repression of SP-D and acquisition of an EMT phenotype. Thus this is the first study to demonstrate the molecular mechanisms, in which SP-D expression under acute and persistent hypoxia in acute lung injury might be differentially modulated by stabilized HIF-1α expression and de novo twist expression.

scholarly journals Surfactant Protein D Protects Against Hyperoxia‐Induced Acute Lung Injury In A Murine Model

2006 ◽  
Vol 20 (5) ◽  
Author(s):  
Deepika Jain ◽  
Elena N. Atochina‐Vasserman ◽  
Helchem Kadire ◽  
Yaniv Tomer ◽  
Adam Inch ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Murine Model ◽  
Surfactant Protein ◽  
Surfactant Protein D

scholarly journals Lower Oligomeric Form of Surfactant Protein D in Murine Acute Lung Injury Induces M1 Subtype Macrophages Through Calreticulin/p38 MAPK Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Dandan Li ◽  
Linyue Pan ◽  
Xiaoju Zhang ◽  
Zhilong Jiang
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Signaling Pathway ◽  
Surfactant Protein ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Tnf Alpha ◽  
Surfactant Protein D ◽  
Downstream Signaling ◽  
Oligomeric Form

Surfactant protein D (SP-D) plays an important role in innate and adaptive immune responses. In this study, we found that the expression of total and de-oligomerized SP-D was significantly elevated in mice with lipopolysaccharide (LPS)-induced acute lung injury (ALI). To investigate the role of the lower oligomeric form of SP-D in the pathogenesis of ALI, we treated bone marrow-derived macrophages (BMDMs) with ALI-derived bronchoalveolar lavage (BAL) and found that SP-D in ALI BAL predominantly bound to calreticulin (CALR) on macrophages, subsequently increasing the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and expression of interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, IL-10, and CD80. However, anti-SP-D (aSP-D) and anti-calreticulin (aCALR) pretreatment reversed the SP-D binding and activation of macrophages induced by ALI BAL or de-oligomerized recombinant murine SP-D (rSP-D). Lack of signal transducer and activator of transcription (STAT)6 in STAT6-/- macrophages resulted in resistance to suppression by aCALR. Further studies in an ALI mouse model showed that blockade of pulmonary SP-D by intratracheal (i.t.), but not intraperitoneal (i.p.), administration of aSP-D attenuated the severity of ALI, accompanied by lower neutrophil infiltrates and expression of IL-1beta and IL-6. Furthermore, i.t. administration of de-oligomerized rSP-D exacerbated the severity of ALI in association with more pro-inflammatory CD45+Siglec-F(-) M1 subtype macrophages and production of IL-6, TNF-alpha, IL-1beta, and IL-18. The results indicated that SP-D in the lungs of murine ALI was de-oligomerized and participated in the pathogenesis of ALI by predominantly binding to CALR on macrophages and subsequently activating the pro-inflammatory downstream signaling pathway. Targeting de-oligomerized SP-D is a promising therapeutic strategy for the treatment of ALI and acute respiratory distress syndrome (ARDS).

Surfactant protein D is a useful biomarker for monitoring acute lung injury in rats

2016 ◽  
Vol 42 (6) ◽  
pp. 314-321 ◽  
Author(s):  
Makoto Murata ◽  
Mitsuo Otsuka ◽  
Noriyuki Ashida ◽  
Gen Yamada ◽  
Koji Kuronuma ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Surfactant Protein ◽  
Surfactant Protein D

scholarly journals Surfactant Protein D Is Altered in Experimental Malaria-Associated Acute Lung Injury/Acute Respiratory Distress Syndrome

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Chuchard Punsawad ◽  
Parnpen Viriyavejakul ◽  
Tachpon Techarang
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Malaria Infection ◽  
Immunohistochemical Staining ◽  
Distress Syndrome ◽  
Surfactant Protein ◽  
Lung Homogenate ◽  
Surfactant Protein D ◽  
Control Group

Surfactant protein D (SP-D) is in the collectin family of C-type lectins and plays an important role in the regulation of inflammation and the innate immune defense against pathogens. This protein has been proposed as a biomarker for acute lung injury. However, the expression of SP-D in the lung and the circulating levels of SP-D during malaria infection have received limited attention. Therefore, the aim of this study was to determine the location and expression of the SP-D protein in lung tissue and to measure the plasma level of SP-D in experimental malaria-associated acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Malaria-infected mice induced by Plasmodium berghei ANKA were classified into two groups, namely, the ALI/ARDS and non-ALI/ARDS groups, according to lung histopathology. The lungs of uninfected mice were used as a control group. The location and expression of SP-D in the lung tissues were investigated by immunohistochemical staining and Western blot analysis. In addition, the level of SP-D in plasma and lung homogenate was measured by an enzyme-linked immunosorbent assay. Immunohistochemical staining of SP-D was significantly increased in the lung tissues of the malaria-infected mice in the ALI/ARDS group compared with that in the malaria-infected mice in the non-ALI/ARDS group and the mice in the control group (p < 0.05). The levels of SP-D in the plasma and lung homogenate were significantly increased in the malaria-infected mice in the ALI/ARDS group compared with those in the malaria-infected mice in the non-ALI/ARDS group and the mice in the control group (p < 0.05). There was a significant positive correlation between SP-D in the plasma and SP-D in the lung homogenate (rs = 0.900, p = 0.037). In conclusion, this study demonstrated increased expression levels of SP-D in the lung tissue and high levels of plasma SP-D in the malaria-infected mice with ALI/ARDS compared with those in the mice in the other groups. The current study supports that the elevation of the plasma SP-D level may provide useful biological confirmation of the diagnosis of ALI/ARDS during malaria infection.

SURFACTANT PROTEIN D (SP-D) IN PAEDIATRIC ACUTE LUNG INJURY (ALI)

2004 ◽  
Vol 32 (Supplement) ◽  
pp. A116
Author(s):  
Michael J Marsh ◽  
Neil G Henderson ◽  
Anne George ◽  
Anthony D Postle ◽  
David A Todd ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Surfactant Protein ◽  
Surfactant Protein D

scholarly journals Endothelial-to-mesenchymal transition in lipopolysaccharide-induced acute lung injury drives a progenitor cell-like phenotype

2016 ◽  
Vol 310 (11) ◽  
pp. L1185-L1198 ◽  
Author(s):  
Toshio Suzuki ◽  
Yuji Tada ◽  
Rintaro Nishimura ◽  
Takeshi Kawasaki ◽  
Ayumi Sekine ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Endothelial Cells ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Vascular Endothelial Cells ◽  
Repair Process ◽  
Vascular Endothelial ◽  
Mesenchymal Transition ◽  
Oxidase Inhibition ◽  
Endothelial To Mesenchymal Transition

Pulmonary vascular endothelial function may be impaired by oxidative stress in endotoxemia-derived acute lung injury. Growing evidence suggests that endothelial-to-mesenchymal transition (EndMT) could play a pivotal role in various respiratory diseases; however, it remains unclear whether EndMT participates in the injury/repair process of septic acute lung injury. Here, we analyzed lipopolysaccharide (LPS)-treated mice whose total number of pulmonary vascular endothelial cells (PVECs) transiently decreased after production of reactive oxygen species (ROS), while the population of EndMT-PVECs significantly increased. NAD(P)H oxidase inhibition suppressed EndMT of PVECs. Most EndMT-PVECs derived from tissue-resident cells, not from bone marrow, as assessed by mice with chimeric bone marrow. Bromodeoxyuridine-incorporation assays revealed higher proliferation of capillary EndMT-PVECs. In addition, EndMT-PVECs strongly expressed c- kit and CD133. LPS loading to human lung microvascular endothelial cells (HMVEC-Ls) induced reversible EndMT, as evidenced by phenotypic recovery observed after removal of LPS. LPS-induced EndMT-HMVEC-Ls had increased vasculogenic ability, aldehyde dehydrogenase activity, and expression of drug resistance genes, which are also fundamental properties of progenitor cells. Taken together, our results demonstrate that LPS induces EndMT of tissue-resident PVECs during the early phase of acute lung injury, partly mediated by ROS, contributing to increased proliferation of PVECs.

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