Surfactant protein-D deficiency suppresses systemic inflammation and reduces atherosclerosis in ApoE knockout mice

Hirano, Yuki; Choi, Alex GoEun; Tsuruta, Masashi; Jaw, Jen Erh; Oh, Yeni; Ngan, David A.; Moritani, Konosuke; Chen, Yu Wei Roy; Tam, Sheena; Li, Yuexin; Vasilescu, Dragoş M.; Hogg, James C.; Bernatchez, Pascal; Man, S. F. Paul; Sin, Don D.

doi:10.1093/cvr/cvx067

Cited by 16 publications

(25 citation statements)

References 48 publications

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“…A subsequent study using double-deficient apolipoprotein E ( Apoe ) −/− Sftpd −/− mice showed similar quantitative effects in decreasing lesion size. Moreover, Sftpd deficiency resulted in less macrophage accumulation, and more smooth muscle cell coverage of lesions ( 457 ). In that study, endogenous SP-D reduced several plasma lipid fractions, including total cholesterol and induced circulatory IL-6, rather than TNF-α.…”

Section: Sp-d In Non-respiratory Diseasesmentioning

confidence: 99%

“…The simplified overview of cellular functions in atherogenesis was inspired by Skaggs et al ( 458 ). Effects of SP-D in a long-term diet-induced model of atherosclerosis include (1) repression of high-density lipoprotein (HDL)-cholesterol levels ( 48 ) and also additional plasma lipid levels in a genetic model ( 457 ); (2) model-dependent induction of tumor necrosis factor-α (TNF-α) in vivo ( 48 , 457 ) and TNF-α induction in monocytes in vitro , dependent on osteoclast-associated receptor (OSCAR) signaling ( 133 ); (3) induction of macrophage proliferation ( 457 ); (4) induction of circulating monocytes; (5) decreased coverage of smooth muscle in plaques ( 457 ); (6) the result is an overall increase in atherosclerotic plaque formation with accumulation of foam cells and cholesterol crystals, accompanied by disturbed plasma lipid levels in Sftpd −/− mice compared with Sftpd +/+ mice ( 48 , 457 ). Moreover, TNF-α and NO increase endothelial SP-D expression ( 63 ) and circulating SP-D is increased in clinical cardiovascular disease (CVD) ( 25 , 429 ).…”

Section: Sp-d In Non-respiratory Diseasesmentioning

confidence: 99%

“…Three independent studies have demonstrated a link between Sftpd deficiency and obesity ( 457 , 476 , 478 ). According to a study by Stidsen et al ( 478 ), body mass development in Sftpd -deficient mice was significantly increased compared with that of corresponding wild-type mice receiving both ad libitum and fixed energy intake diets.…”

Section: Sp-d In Non-respiratory Diseasesmentioning

confidence: 99%

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Surfactant Protein D in Respiratory and Non-Respiratory Diseases

2018

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Surfactant protein D (SP-D) is a multimeric collectin that is involved in innate immune defense and expressed in pulmonary, as well as non-pulmonary, epithelia. SP-D exerts antimicrobial effects and dampens inflammation through direct microbial interactions and modulation of host cell responses via a series of cellular receptors. However, low protein concentrations, genetic variation, biochemical modification, and proteolytic breakdown can induce decomposition of multimeric SP-D into low-molecular weight forms, which may induce pro-inflammatory SP-D signaling. Multimeric SP-D can decompose into trimeric SP-D, and this process, and total SP-D levels, are partly determined by variation within the SP-D gene, SFTPD. SP-D has been implicated in the development of respiratory diseases including respiratory distress syndrome, bronchopulmonary dysplasia, allergic asthma, and chronic obstructive pulmonary disease. Disease-induced breakdown or modifications of SP-D facilitate its systemic leakage from the lung, and circulatory SP-D is a promising biomarker for lung injury. Moreover, studies in preclinical animal models have demonstrated that local pulmonary treatment with recombinant SP-D is beneficial in these diseases. In recent years, SP-D has been shown to exert antimicrobial and anti-inflammatory effects in various non-pulmonary organs and to have effects on lipid metabolism and pro-inflammatory effects in vessel walls, which enhance the risk of atherosclerosis. A common SFTPD polymorphism is associated with atherosclerosis and diabetes, and SP-D has been associated with metabolic disorders because of its effects in the endothelium and adipocytes and its obesity-dampening properties. This review summarizes and discusses the reported genetic associations of SP-D with disease and the clinical utility of circulating SP-D for respiratory disease prognosis. Moreover, basic research on the mechanistic links between SP-D and respiratory, cardiovascular, and metabolic diseases is summarized. Perspectives on the development of SP-D therapy are addressed.

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Section: Sp-d In Non-respiratory Diseasesmentioning

confidence: 99%

Section: Sp-d In Non-respiratory Diseasesmentioning

confidence: 99%

Section: Sp-d In Non-respiratory Diseasesmentioning

confidence: 99%

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Surfactant Protein D in Respiratory and Non-Respiratory Diseases

2018

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“…Although the relationship between SP-D and monocytes remains unclear, Jiang et al reported that depletion of circulating monocytes by intravenous injection of CL 2 days before intratracheal lipopolysaccharide (LPS) treatment significantly reduced SP-D in the lungs of mice treated with intratracheal LPS for 2 days (27) and Hirano et al reported that SP-D deficiency reduced blood monocytes in atherosclerosis-prone apolipoprotein E-knockout mice (28) . We therefore considered that elevation of SP-D was involved in the elevation of monocytes, and that the development of fibrosis associated with monocyte activation played a role in the relapse of OP.…”

Section: Discussionmentioning

confidence: 99%

Organizing pneumonia with elevated surfactant protein-D needs attention to the possibility of relapse

Yamagishi

Kodaka

Watanabe

et al. 2019

Preprint

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Background and Objectives Organizing pneumonia (OP) usually responds spectacularly well to initial treatment, but relapses can occur and some cases run a fatal course. Still the issue of relapse has been addressed in relatively few studies and predictors have not been clarified. The purpose of this study was to examine the pattern of relapses in OP, to determine whether relapse affects morbidity and mortality and to identify possible predictors of relapse. Methods Blood sampling, pulmonary function testing, computed tomography (CT) of the chest and bronchofiberscopy were performed for all patients and were retrospectively reviewed along with clinical information. To determine relapse of OP, additional chest CT was performed regularly or when relapse of OP was clinically suspected. All patients were followed regarding treatment response, treatment duration and presence of relapse. Results were compared between two groups based on serum concentrations of surfactant protein (SP)-D: normal SP-D; and high SP-D. Results Twenty-two patients were analyzed in this study. SP-D showed a negative correlation with percutaneous oxygen saturation, and positive correlations with serum lactate dehydrogenase (LDH), Krebs von den Lungen (KL)-6 and percentage lymphocytes in bronchoalveolar lavage (BAL). Prognosis was good for all patients, but relapse was significantly more frequent in the high SP-D group (6 cases) than in the normal SP-D group (0 cases; p=0.049). Serum KL-6 and percentage monocytes in BAL were significantly higher and pulmonary vital capacity and forced expiratory volume in 1 s were significantly lower in the high SP-D group than in the low SP-D group. Conclusions When treating cases of OP with high serum concentrations of SP-D, attention should be paid to the possibility of relapse.

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“…We used C57BL/6 female mice that were purchased from CLEA Japan. SP-D knockout mice were kindly provided by Dr Don D. Sin in Vancouver, Canada ( 16 ). DNA was extracted from tail biopsies of mice using DNeasy blood and tissue kit (Qiagen, Inc.), according to the manufacturer's protocol.…”

Section: Methodsmentioning

confidence: 99%

Association of surfactant protein D with pulmonary metastases from colon cancer

et al. 2020

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Surfactant protein D (SP-D) is a member of the collectin family of proteins, which is secreted by airway epithelial cells. SP-D serves an important role in the immune system and in the inflammatory regulation of the lung. SP-D was recently found to suppress lung cancer progression by downregulating epidermal growth factor signaling. However, the relationship between SP-D and pulmonary metastases from colon cancer remains unknown. The present study aimed to determine whether SP-D may suppress the development of the mouse rectal carcinoma cell line, CMT93, in vitro . The present study investigated the effect of SP-D on pulmonary metastases from colon cancer in vivo using SP-D knockout mice. A wound healing assay and cell invasion assay revealed that SP-D suppressed the proliferation, migration and invasion of CMT-93 cells. After injection of CMT-93 cells into the tail vein, SP-D knockout mice were significantly more susceptible to developing pulmonary metastases than C57/BL6 mice (control). Moreover, a novel cell line (CMT-93 pulmonary metastasis; CMT-93 PM) was established from the lesions of pulmonary metastases in C57/BL6 mice following injection of CMT93 into the tail vein. CMT-93 PM exhibited more robust invasion and proliferation compared to CMT93, which was unaffected by exposure to SP-D. A higher incidence of pulmonary metastases was detected following injection of CMT93 PM into the tail vein of C57/BL6 mice compared with CMT-93. Consequently, SP-D may be involved in the pathogenesis of pulmonary metastases from colon cancer.

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Surfactant protein-D deficiency suppresses systemic inflammation and reduces atherosclerosis in ApoE knockout mice

Cited by 16 publications

References 48 publications

Surfactant Protein D in Respiratory and Non-Respiratory Diseases

Surfactant Protein D in Respiratory and Non-Respiratory Diseases

Organizing pneumonia with elevated surfactant protein-D needs attention to the possibility of relapse

Association of surfactant protein D with pulmonary metastases from colon cancer

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Surfactant protein-D deficiency suppresses systemic inflammation and reduces atherosclerosis in ApoE knockout mice

Cited by 16 publications

References 48 publications

Surfactant Protein D in Respiratory and Non-Respiratory Diseases

Surfactant Protein D in Respiratory and Non-Respiratory Diseases

Organizing pneumonia with elevated surfactant protein-D needs attention to the possibility of relapse

Association of surfactant protein&nbsp;D with pulmonary metastases from colon cancer

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Association of surfactant protein D with pulmonary metastases from colon cancer