Localization of surfactant protein‐D in the rheumatoid synovial membrane

Christensen, Anders Lyhne; Sørensen, Grith Lykke; Junker, Kirsten; Revald, Peter; Varnum, Claus; Sørensen, Flemming Brandt; Junker, Peter

doi:10.1111/apm.12785

Cited by 7 publications

(9 citation statements)

References 20 publications

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“…Furthermore, its presence has been demonstrated in healthy lacrimal gland, conjunctiva, cornea, and nasolacrimal duct samples ( 6 ). Other studies have shown the presence of SP-D in synovial fluid derived from patients with rheumatoid arthritis ( 7 ).…”

Section: Introductionmentioning

confidence: 91%

Pathological Significance and Prognostic Value of Surfactant Protein D in Cancer

et al. 2018

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Surfactant protein D (SP-D) is a pattern recognition molecule belonging to the Collectin (collagen-containing C-type lectin) family that has pulmonary as well as extra-pulmonary existence. In the lungs, it is a well-established opsonin that can agglutinate a range of microbes, and enhance their clearance via phagocytosis and super-oxidative burst. It can interfere with allergen–IgE interaction and suppress basophil and mast cell activation. However, it is now becoming evident that SP-D is likely to be an innate immune surveillance molecule against tumor development. SP-D has been shown to induce apoptosis in sensitized eosinophils derived from allergic patients and a leukemic cell line via p53 pathway. Recently, SP-D has been shown to suppress lung cancer progression via interference with the epidermal growth factor signaling. In addition, a truncated form of recombinant human SP-D has been reported to induce apoptosis in pancreatic adenocarcinoma via Fas-mediated pathway in a p53-independent manner. To further establish a correlation between SP-D presence/levels and normal and cancer tissues, we performed a bioinformatics analysis, using Oncomine dataset and the survival analysis platforms Kaplan–Meier plotter, to assess if SP-D can serve as a potential prognostic marker for human lung cancer, in addition to human gastric, breast, and ovarian cancers. We also analyzed immunohistochemically the presence of SP-D in normal and tumor human tissues. We conclude that (1) in the lung, gastric, and breast cancers, there is a lower expression of SP-D than normal tissues; (2) in ovarian cancer, there is a higher expression of SP-D than normal tissue; and (3) in lung cancer, the presence of SP-D could be associated with a favorable prognosis. On the contrary, at non-pulmonary sites such as gastric, breast, and ovarian cancers, the presence of SP-D could be associated with unfavorable prognosis. Correlation between the levels of SP-D and overall survival requires further investigation. Our analysis involves a large number of dataset; therefore, any trend observed is reliable. Despite apparent complexity within the results, it is evident that cancer tissues that produce less levels of SP-D compared to their normal tissue counterparts are probably less susceptible to SP-D-mediated immune surveillance mechanisms via infiltrating immune cells.

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Section: Introductionmentioning

confidence: 91%

Pathological Significance and Prognostic Value of Surfactant Protein D in Cancer

et al. 2018

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“…SP-D is primarily synthesized and secreted into the airspace of the lungs by alveolar type II and Clara cells, with a key role in surfactant homeostasis by reducing surface tension ( 6 ). However, its extrapulmonary existence is well-established now, ranging from the mucosa of the gastrointestinal and reproductive tracts (including ovaries) and nasal cavity to the brain and in various exocrine ducts ( 8 , 9 ), conjunctiva, cornea, lacrimal gland, nasolacrimal ducts ( 8 ), and synovial fluid ( 10 ). Protective effects of SP-D against a range of pathogens ( 6 , 11 ) and allergens ( 12 – 16 ) are well-documented in the literature.…”

Section: Introductionmentioning

confidence: 99%

Hyaluronic Acid Present in the Tumor Microenvironment Can Negate the Pro-apototic Effect of a Recombinant Fragment of Human Surfactant Protein D on Breast Cancer Cells

et al. 2020

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Human surfactant protein D (SP-D) belongs to the family of collectins that is composed of a characteristic amino-terminal collagenous region and a carboxy-terminal C-type lectin domain. Being present at the mucosal surfaces, SP-D acts as a potent innate immune molecule and offers protection against non-self and altered self, such as pathogens, allergens, and tumor. Here, we examined the effect of a recombinant fragment of human SP-D (rfhSP-D) on a range of breast cancer lines. Breast cancer has four molecular subtypes characterized by varied expressions of estrogen (ER), progesterone (PR), and epidermal growth factor (EGF) receptors (HER2). The cell viability of HER2-overexpressing (SKBR3) and triple-positive (BT474) breast cancer cell lines [but not of a triple-negative cell line (BT20)] was reduced following rfhSP-D treatment at 24 h. Upregulation of p21/p27 cell cycle inhibitors and p53 phosphorylation (Ser15) in rfhSP-D-treated BT474 and SKBR3 cell lines signified G2/M cell cycle arrest. Cleaved caspases 9 and 3 were detected in rfhSP-D-treated BT474 and SKBR3 cells, suggesting an involvement of the intrinsic apoptosis pathway. However, rfhSP-D-induced apoptosis was nullified in the presence of hyaluronic acid (HA) whose increased level in breast tumor microenvironment is associated with malignant tumor progression and invasion. rfhSP-D bound to solid-phase HA and promoted tumor cell proliferation. rfhSP-D-treated SKBR3 cells in the presence of HA showed decreased transcriptional levels of p53 when compared to cells treated with rfhSP-D only. Thus, HA appears to negate the anti-tumorigenic properties of rfhSP-D against HER2-overexpressing and triple-positive breast cancer cells.

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“…1 Decreased SP-D levels in early RA may correlate negatively to RA disease activity measures 41 42 and may modulate inflammation in RA. 43 Increased serum microfibrillar-associated protein 4 (MFAP4) seem to reflect disease-induced processes, due to low heritability and relatively limited basal variation. 44 MFAP4 is found with especially high expression in the heart, small intestine and the lungs.…”

Section: Potential Blood Biomarkers (Ie Other Index Tests)mentioning

confidence: 99%

“… 1 Decreased SP-D levels in early RA may correlate negatively to RA disease activity measures 41 42 and may modulate inflammation in RA. 43 …”

Section: Introductionmentioning

confidence: 99%

Using thoracic ultrasound to detect interstitial lung disease in patients with rheumatoid arthritis: a protocol for the diagnostic test accuracy AURORA study

et al. 2022

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IntroductionPulmonary diseases are significant contributors to morbidity and mortality in patients with rheumatoid arthritis (RA). RA-associated interstitial lung disease (RA-ILD) may be prevalent in up to 30% and clinically evident in 10% of patients with RA. Feasible methods to detect concomitant ILD in RA are warranted. Our objective is to determine the diagnostic accuracy of thoracic ultrasound (TUS) for ILD in patients with RA with respiratory symptoms, by using chest high-resolution CT (HRCT) as the reference standard. Further, we aim to evaluate the diagnostic accuracy for the promising blood biomarkers surfactant protein-D and microfibrillar-associated protein 4 in the detection of ILD in this group of patients.Methods and analysisBy use of a standardised 14 zone protocol patients suspected of having RA-ILD will undergo TUS as index test performed by a junior resident in rheumatology (BKS), who is certified by the European Respiratory Society in performing TUS assessments. Participants form a consecutive series of up to 80 individuals in total. The anonymised TUS images will be stored and scored by the junior resident as well as two senior rheumatologists, who have received training in TUS, and a TUS-experienced pulmonologist. HRCT will be used as the gold standard for ILD diagnosis (reference standard). The two basic measures for quantifying the diagnostic test accuracy of the TUS test are the sensitivity and specificity in comparison to the HRCT.Ethics and disseminationData will be collected and stored in the Research Electronic Data Capture database. The study is approved by the Committees on Health Research Ethics and the Danish Data Protection Agency. The project is registered at clinicaltrials.gov (NCT05396469, pre-results) and data will be published in peer-reviewed journals.

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Localization of surfactant protein‐D in the rheumatoid synovial membrane

Cited by 7 publications

References 20 publications

Pathological Significance and Prognostic Value of Surfactant Protein D in Cancer

Pathological Significance and Prognostic Value of Surfactant Protein D in Cancer

Hyaluronic Acid Present in the Tumor Microenvironment Can Negate the Pro-apototic Effect of a Recombinant Fragment of Human Surfactant Protein D on Breast Cancer Cells

Using thoracic ultrasound to detect interstitial lung disease in patients with rheumatoid arthritis: a protocol for the diagnostic test accuracy AURORA study

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